Stem cells

  • Article
    | Open Access

    Methods to generate beige adipocytes from a human cell source are inefficient. Here, the authors present a protocol that efficiently generates beige adipocytes from human adipose-derived stem cells (ADSCs), which have potential utility in therapeutic development relating to metabolic diseases such as type 2 diabetes.

    • Amar M. Singh
    • , Liang Zhang
    • , John Avery
    • , Amelia Yin
    • , Yuhong Du
    • , Hui Wang
    • , Zibo Li
    • , Haian Fu
    • , Hang Yin
    •  & Stephen Dalton
  • Article
    | Open Access

    The MAF bZIP transcription factor B (MAFB) is present in postnatal human beta cells but its role is unclear. Here, the authors show that MAFB regulates endocrine pancreatic cell fate specification.

    • Ronan Russell
    • , Phichitpol P. Carnese
    • , Thomas G. Hennings
    • , Emily M. Walker
    • , Holger A. Russ
    • , Jennifer S. Liu
    • , Simone Giacometti
    • , Roland Stein
    •  & Matthias Hebrok
  • Article
    | Open Access

    Long noncoding RNA SAM (Sugt1 associated muscle) is upregulated in the proliferating myoblast cells. Here the authors investigate SAM knockout mice and suggest that SAM binds and stabilizes Sugt1, a co-chaperone protein that regulates kinetochore assembly.

    • Yuying Li
    • , Jie Yuan
    • , Fengyuan Chen
    • , Suyang Zhang
    • , Yu Zhao
    • , Xiaona Chen
    • , Leina Lu
    • , Liang Zhou
    • , Ching Yan Chu
    • , Hao Sun
    •  & Huating Wang
  • Article
    | Open Access

    Until now, the transcriptome of preimplantation mouse embryos has only been analysed by short-read sequencing. Here, the authors perform long-read sequencing to provide a more detailed transcriptome of the preimplantation mouse embryo, identifying various novel transcripts, for example Kdm4dl.

    • Yunbo Qiao
    • , Chao Ren
    • , Shisheng Huang
    • , Jie Yuan
    • , Xingchen Liu
    • , Jiao Fan
    • , Jianxiang Lin
    • , Susu Wu
    • , Qiuzhen Chen
    • , Xiaochen Bo
    • , Xiangyang Li
    • , Xingxu Huang
    • , Zhen Liu
    •  & Wenjie Shu
  • Article
    | Open Access

    The mechanisms regulating regeneration of the earthworm are unclear. Here, the authors use genomic and transcriptomic analysis of the earthworm Eisenia andrei together with Hi-C analysis to identify genes involved and show activation of LINE2 transposable elements on regeneration.

    • Yong Shao
    • , Xiao-Bo Wang
    • , Jin-Jin Zhang
    • , Ming-Li Li
    • , Shou-Song Wu
    • , Xi-Yao Ma
    • , Xue Wang
    • , Hui-Fang Zhao
    • , Yuan Li
    • , Helen He Zhu
    • , David M. Irwin
    • , De-Peng Wang
    • , Guo-Jie Zhang
    • , Jue Ruan
    •  & Dong-Dong Wu
  • Article
    | Open Access

    The DIS3L2 exonuclease degrades aberrant 7SL RNAs tagged by an oligouridine 3′-tail. Here the authors analyze DIS3L2 knockout mouse embryonic stem cells and suggest that DIS3L2-mediated quality control of 7SL RNA is important for ER-mediated translation and calcium ion homeostasis.

    • Mehdi Pirouz
    • , Chih-Hao Wang
    • , Qi Liu
    • , Aref G. Ebrahimi
    • , Farnaz Shamsi
    • , Yu-Hua Tseng
    •  & Richard I. Gregory
  • Article
    | Open Access

    The molecular mechanisms that regulate intestinal Clu+ revival stem cells (revSCs) and their niche to enable regeneration in response to injury are unclear. Here, the authors show that mice without the phospholipid transport protein, TNFAIP8, causes less revSCs to be induced following injury.

    • Jason R. Goldsmith
    • , Nina Spitofsky
    • , Ali Zamani
    • , Ryan Hood
    • , Amanda Boggs
    • , Xinyuan Li
    • , Mingyue Li
    • , Elizabeth Reiner
    • , Arshad Ayyaz
    • , Zienab Etwebi
    • , Ling Lu
    • , Javier Rivera Guzman
    • , Mayassa J. Bou-Dargham
    • , Terry Cathoupolis
    • , Hakon Hakonarson
    • , Honghong Sun
    • , Jeffrey L. Wrana
    • , Michael V. Gonzalez
    •  & Youhai H. Chen
  • Article
    | Open Access

    Genetic changes acquired during in vitro culture pose a challenge to application of stem cells. Here the authors use whole genome sequencing to show that cultured human adult and pluripotent stem cells have a high mutational load caused by oxidative stress and reduced oxygen tension in culture lowers mutation rates.

    • Ewart Kuijk
    • , Myrthe Jager
    • , Bastiaan van der Roest
    • , Mauro D. Locati
    • , Arne Van Hoeck
    • , Jerome Korzelius
    • , Roel Janssen
    • , Nicolle Besselink
    • , Sander Boymans
    • , Ruben van Boxtel
    •  & Edwin Cuppen
  • Article
    | Open Access

    Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

    • Katherine C. Goldfarbmuren
    • , Nathan D. Jackson
    • , Satria P. Sajuthi
    • , Nathan Dyjack
    • , Katie S. Li
    • , Cydney L. Rios
    • , Elizabeth G. Plender
    • , Michael T. Montgomery
    • , Jamie L. Everman
    • , Preston E. Bratcher
    • , Eszter K. Vladar
    •  & Max A. Seibold
  • Article
    | Open Access

    The Transcription Factor EB (TFEB) is known to regulate cellular homeostasis and energy metabolism, but its role in cell fate determination in the liver is unknown. Here, the authors show that TFEB regulates the progenitor/cholangiocyte lineage and that its depletion prevents tissue recovery upon injury.

    • Nunzia Pastore
    • , Tuong Huynh
    • , Niculin J. Herz
    • , Alessia Calcagni’
    • , Tiemo J. Klisch
    • , Lorenzo Brunetti
    • , Kangho Ho Kim
    • , Marco De Giorgi
    • , Ayrea Hurley
    • , Annamaria Carissimo
    • , Margherita Mutarelli
    • , Niya Aleksieva
    • , Luca D’Orsi
    • , William R. Lagor
    • , David D. Moore
    • , Carmine Settembre
    • , Milton J. Finegold
    • , Stuart J. Forbes
    •  & Andrea Ballabio
  • Article
    | Open Access

    What happens to cells on engrafting into the brain in animal models to treat Parkinson’s disease is unclear. Here, the authors use scRNA-seq to examine ventral midbrain (VM)-patterned human embryonic stem cells after functional maturation in a pre-clinical rat model for Parkinson’s disease and identify perivascular-like cells.

    • Katarína Tiklová
    • , Sara Nolbrant
    • , Alessandro Fiorenzano
    • , Åsa K. Björklund
    • , Yogita Sharma
    • , Andreas Heuer
    • , Linda Gillberg
    • , Deirdre B. Hoban
    • , Tiago Cardoso
    • , Andrew F. Adler
    • , Marcella Birtele
    • , Hilda Lundén-Miguel
    • , Nikolaos Volakakis
    • , Agnete Kirkeby
    • , Thomas Perlmann
    •  & Malin Parmar
  • Article
    | Open Access

    Human pluripotent cells (hPSCs) in standard culture are similar to mouse epiblast cells, but heterogeneity within hPSC cultures complicates comparisons. Here the authors show that a subpopulation of hPSCs enriched for self-renewal capacity have distinct cell cycle, metabolic, DNA methylation, and ATAC-seq profiles.

    • Kevin X. Lau
    • , Elizabeth A. Mason
    • , Joshua Kie
    • , David P. De Souza
    • , Joachim Kloehn
    • , Dedreia Tull
    • , Malcolm J. McConville
    • , Andrew Keniry
    • , Tamara Beck
    • , Marnie E. Blewitt
    • , Matthew E. Ritchie
    • , Shalin H. Naik
    • , Daniela Zalcenstein
    • , Othmar Korn
    • , Shian Su
    • , Irene Gallego Romero
    • , Catrina Spruce
    • , Christopher L. Baker
    • , Tracy C. McGarr
    • , Christine A. Wells
    •  & Martin F. Pera
  • Article
    | Open Access

    The downstream pathway regulating how TGF-beta affects pluripotency of human PSCs is unclear. Here, the authors find that transcription factor ZNF398 binds active promoters/enhancers together with the histone acetyltransferase EP300 and SMAD3, enabling expression of pluripotency and epithelial genes.

    • Irene Zorzan
    • , Marco Pellegrini
    • , Mattia Arboit
    • , Danny Incarnato
    • , Mara Maldotti
    • , Mattia Forcato
    • , Guidantonio Malagoli Tagliazucchi
    • , Elena Carbognin
    • , Marco Montagner
    • , Salvatore Oliviero
    •  & Graziano Martello
  • Article
    | Open Access

    Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

    • Quinn P. Peterson
    • , Adrian Veres
    • , Lihua Chen
    • , Michael Q. Slama
    • , Jennifer H. R. Kenty
    • , Shaimaa Hassoun
    • , Matthew R. Brown
    • , Haiqiang Dou
    • , Caden D. Duffy
    • , Quan Zhou
    • , Aleksey V. Matveyenko
    • , Björn Tyrberg
    • , Maria Sörhede-Winzell
    • , Patrik Rorsman
    •  & Douglas A. Melton
  • Article
    | Open Access

    Single-cell RNA-seq can reveal accurate and precise cell types and states. Here the authors present an scRNA-seq platform, Paired-seq, which uses differential flow resistance to achieve 95% cell utilisation efficiency for improved cell-free RNA removal and gene detection.

    • Mingxia Zhang
    • , Yuan Zou
    • , Xing Xu
    • , Xuebing Zhang
    • , Mingxuan Gao
    • , Jia Song
    • , Peifeng Huang
    • , Qin Chen
    • , Zhi Zhu
    • , Wei Lin
    • , Richard N. Zare
    •  & Chaoyong Yang
  • Article
    | Open Access

    How epigenetic regulation affects pancreatic development is unclear. Here, the authors show that the histone demethylase LSD1 regulates the epigenetic state of developmental enhancers during pancreatic specification and controls how these enhancers respond to extracellular signals, namely retinoic acid.

    • Nicholas K. Vinckier
    • , Nisha A. Patel
    • , Ryan J. Geusz
    • , Allen Wang
    • , Jinzhao Wang
    • , Ileana Matta
    • , Austin R. Harrington
    • , Matthew Wortham
    • , Nichole Wetton
    • , Jianxun Wang
    • , Ulupi S. Jhala
    • , Michael G. Rosenfeld
    • , Christopher W. Benner
    • , Hung-Ping Shih
    •  & Maike Sander
  • Article
    | Open Access

    Classical human dendritic cells (cDCs) are rare sentinel cells specialized in regulating adaptive immunity. Here, the authors show that expression of membrane bound FLT3L, along with stem cell factor (SCF) and CXCL12 in stromal cells induces specification of pre/AS-DCs, type 1 and type2 cDC from haematopoietic stem cells.

    • Giorgio Anselmi
    • , Kristine Vaivode
    • , Charles-Antoine Dutertre
    • , Pierre Bourdely
    • , Yoann Missolo-Koussou
    • , Evan Newell
    • , Oliver Hickman
    • , Kristie Wood
    • , Alka Saxena
    • , Julie Helft
    • , Florent Ginhoux
    •  & Pierre Guermonprez
  • Article
    | Open Access

    The identification of mRNA targets for RNA binding proteins (RBP) in stem cells is difficult due to the limited number of available cells. Here, as a proof-of-principle, the authors adapt the HyperTRIBE method to find that an RBP, MSI2, has increased RNA binding in leukemic compared with normal stem cells for selective regulation of oncogenic genes.

    • Diu T. T. Nguyen
    • , Yuheng Lu
    • , Karen L. Chu
    • , Xuejing Yang
    • , Sun-Mi Park
    • , Zi-Ning Choo
    • , Christopher R. Chin
    • , Camila Prieto
    • , Alexandra Schurer
    • , Ersilia Barin
    • , Angela M. Savino
    • , Saroj Gourkanti
    • , Payal Patel
    • , Ly P. Vu
    • , Christina S. Leslie
    •  & Michael G. Kharas
  • Article
    | Open Access

    Epithelial gene expression has been shown to be zonated along the crypt-villus axis, but mechanisms shaping this spatial variability were unknown. Here, Bahar Halpern et al. uncover zonation of mesenchymal cells, including Lgr5+ telocytes, which regulate epithelial gene expression at the villus tip.

    • Keren Bahar Halpern
    • , Hassan Massalha
    • , Rachel K. Zwick
    • , Andreas E. Moor
    • , David Castillo-Azofeifa
    • , Milena Rozenberg
    • , Lydia Farack
    • , Adi Egozi
    • , Dan R. Miller
    • , Inna Averbukh
    • , Yotam Harnik
    • , Noa Weinberg-Corem
    • , Frederic J. de Sauvage
    • , Ido Amit
    • , Ophir D. Klein
    • , Michal Shoshkes-Carmel
    •  & Shalev Itzkovitz
  • Article
    | Open Access

    Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

    • Matt Ulgherait
    • , Anna Chen
    • , Sophie F. McAllister
    • , Han X. Kim
    • , Rebecca Delventhal
    • , Charlotte R. Wayne
    • , Christian J. Garcia
    • , Yocelyn Recinos
    • , Miles Oliva
    • , Julie C. Canman
    • , Martin Picard
    • , Edward Owusu-Ansah
    •  & Mimi Shirasu-Hiza
  • Article
    | Open Access

    Organoid technology has enabled the generation of several breast cancer organoids. Here, the authors combine propagation of normal human mammary tissues with mass cytometry to evaluate the ability of organoid culture technologies to preserve stem cells and differentiated cell types.

    • Jennifer M. Rosenbluth
    • , Ron C. J. Schackmann
    • , G. Kenneth Gray
    • , Laura M. Selfors
    • , Carman Man-Chung Li
    • , Mackenzie Boedicker
    • , Hendrik J. Kuiken
    • , Andrea Richardson
    • , Jane Brock
    • , Judy Garber
    • , Deborah Dillon
    • , Norman Sachs
    • , Hans Clevers
    •  & Joan S. Brugge
  • Article
    | Open Access

    To model hepatocyte function accurately in vitro, it is necessary to generate and maintain a polarized epithelium. Here, the authors describe a protocol to generate polarized human pluripotent stem cell-derived hepatocyte-like cells (HLCs) to model enteric virus production and drug secretion in vitro.

    • Viet Loan Dao Thi
    • , Xianfang Wu
    • , Rachel L. Belote
    • , Ursula Andreo
    • , Constantin N. Takacs
    • , Joseph P. Fernandez
    • , Luis Andre Vale-Silva
    • , Sarah Prallet
    • , Charlotte C. Decker
    • , Rebecca M. Fu
    • , Bingqian Qu
    • , Kunihiro Uryu
    • , Henrik Molina
    • , Mohsan Saeed
    • , Eike Steinmann
    • , Stephan Urban
    • , Roshni R. Singaraja
    • , William M. Schneider
    • , Sanford M. Simon
    •  & Charles M. Rice
  • Article
    | Open Access

    Translational control of gene expression can lead to significant divergence between mRNA and protein abundance. Here, the authors describe transcriptional rewiring and translational buffering during transition from naïve to primed pluripotency through quantitation of mRNA-abundance, translation rate and protein expression.

    • Yaser Atlasi
    • , Seyed Mehdi Jafarnejad
    • , Christos G. Gkogkas
    • , Michiel Vermeulen
    • , Nahum Sonenberg
    •  & Hendrik G. Stunnenberg
  • Article
    | Open Access

    Whilst pigmentation has been used to identify retinal pigment epithelial (RPE) cells, surface markers for these cells remain unclear. Here, the authors define surface markers for the RPE including CD140b, which help produce hPSC-derived RPE cells at a large scale following a robust, direct and scalable monolayer differentiation protocol.

    • Alvaro Plaza Reyes
    • , Sandra Petrus-Reurer
    • , Sara Padrell Sánchez
    • , Pankaj Kumar
    • , Iyadh Douagi
    • , Hammurabi Bartuma
    • , Monica Aronsson
    • , Sofie Westman
    • , Emma Lardner
    • , Helder André
    • , Anna Falk
    • , Emeline F. Nandrot
    • , Anders Kvanta
    •  & Fredrik Lanner
  • Article
    | Open Access

    Human microglia present unique features; therefore, chimeric mouse models can enhance modelling of human microglia response in health and disease. Here, the authors show that hiPSC-derived mature microglia developed in the mouse brain, retain their identity and respond to demyelination.

    • Ranjie Xu
    • , Xiaoxi Li
    • , Andrew J. Boreland
    • , Anthony Posyton
    • , Kelvin Kwan
    • , Ronald P. Hart
    •  & Peng Jiang
  • Article
    | Open Access

    Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

    • Tapash Jay Sarkar
    • , Marco Quarta
    • , Shravani Mukherjee
    • , Alex Colville
    • , Patrick Paine
    • , Linda Doan
    • , Christopher M. Tran
    • , Constance R. Chu
    • , Steve Horvath
    • , Lei S. Qi
    • , Nidhi Bhutani
    • , Thomas A. Rando
    •  & Vittorio Sebastiano
  • Article
    | Open Access

    Mutations in human pluripotent stem cells (PSC) and whether any form during culture prior to use in a human clinical context are a concern. Here, the authors use hPSCs derived to cGMP standards and show they have low mutation rates after culture, noting this decreases on culturing in low (5%) oxygen conditions.

    • Oliver Thompson
    • , Ferdinand von Meyenn
    • , Zoe Hewitt
    • , John Alexander
    • , Andrew Wood
    • , Richard Weightman
    • , Sian Gregory
    • , Felix Krueger
    • , Simon Andrews
    • , Ivana Barbaric
    • , Paul J. Gokhale
    • , Harry D. Moore
    • , Wolf Reik
    • , Marta Milo
    • , Serena Nik-Zainal
    • , Kosuke Yusa
    •  & Peter W. Andrews
  • Article
    | Open Access

    Hippo TEAD-transcriptional regulators YAP1 and TAZ modulate cell growth, but the downstream networks are unclear. Here, the authors use a genetically-encoded inhibitor of YAP1/TAZ interaction with TEAD (TEADi) to disrupt transcriptional networks for cell cycle and terminal differentiation in human keratinocytes and mouse skin.

    • Yao Yuan
    • , Jeannie Park
    • , Amber Feng
    • , Parirokh Awasthi
    • , Zhiyong Wang
    • , Qianming Chen
    •  & Ramiro Iglesias-Bartolome
  • Article
    | Open Access

    Understanding how cells maintain tissues is challenging. Here, the authors present a single consistent quantitative approach to analyse cell proliferation and lineage tracing data, which shows a single proliferating cell population that maintains epidermal and esophageal epithelial homeostasis.

    • Gabriel Piedrafita
    • , Vasiliki Kostiou
    • , Agnieszka Wabik
    • , Bartomeu Colom
    • , David Fernandez-Antoran
    • , Albert Herms
    • , Kasumi Murai
    • , Benjamin A. Hall
    •  & Philip H. Jones
  • Article
    | Open Access

    Chromatin accessibility is a key mediator of gene expression and mutations in chromatin modifiers are frequently seen in cancers. Here, the authors show that the chromatin accessibility regulator HMGN1 - which is frequently mutated by amplification in leukemias - acts by blocking myeloid differentiation.

    • Lucia Cabal-Hierro
    • , Peter van Galen
    • , Miguel A. Prado
    • , Kelly J. Higby
    • , Katsuhiro Togami
    • , Cody T. Mowery
    • , Joao A. Paulo
    • , Yingtian Xie
    • , Paloma Cejas
    • , Takashi Furusawa
    • , Michael Bustin
    • , Henry W. Long
    • , David B. Sykes
    • , Steven P. Gygi
    • , Daniel Finley
    • , Bradley E. Bernstein
    •  & Andrew A. Lane
  • Article
    | Open Access

    Fgf4 is a critical signal driving embryonic stem cell (ESC) exit from pluripotency and differentiation. Here the authors identify EPHA2 as a target of FGF4 signalling in ESCs, and show that EPHA2-EFNA1 signalling promotes pluripotent gene expression and suppresses commitment through repression of ERK1/2 activation.

    • Rosalia Fernandez-Alonso
    • , Francisco Bustos
    • , Manon Budzyk
    • , Pankaj Kumar
    • , Andreas O. Helbig
    • , Jens Hukelmann
    • , Angus I. Lamond
    • , Fredrik Lanner
    • , Houjiang Zhou
    • , Evangelia Petsalaki
    •  & Greg M. Findlay
  • Article
    | Open Access

    Hepatocytes grown in a dish are immature and do not metabolize compounds as a real liver would. Here, the authors supply stem cell-derived hepatocytes with amino acids at a higher concentration than nutritionally necessary, changing the metabolism of these cells, making them more mature and useful for drug screening and toxicity studies.

    • Ruben Boon
    • , Manoj Kumar
    • , Tine Tricot
    • , Ilaria Elia
    • , Laura Ordovas
    • , Frank Jacobs
    • , Jennifer One
    • , Jonathan De Smedt
    • , Guy Eelen
    • , Matthew Bird
    • , Philip Roelandt
    • , Ginevra Doglioni
    • , Kim Vriens
    • , Matteo Rossi
    • , Marta Aguirre Vazquez
    • , Thomas Vanwelden
    • , François Chesnais
    • , Adil El Taghdouini
    • , Mustapha Najimi
    • , Etienne Sokal
    • , David Cassiman
    • , Jan Snoeys
    • , Mario Monshouwer
    • , Wei-Shou Hu
    • , Christian Lange
    • , Peter Carmeliet
    • , Sarah-Maria Fendt
    •  & Catherine M. Verfaillie
  • Article
    | Open Access

    Pre-clinical cell culture models capturing the heterogeneity of childhood kidney tumours are limited. Here, the authors establish and characterise an organoid biobank of tumour and matched normal organoid cultures from over 50 children with different subtypes of kidney cancer.

    • Camilla Calandrini
    • , Frans Schutgens
    • , Rurika Oka
    • , Thanasis Margaritis
    • , Tito Candelli
    • , Luka Mathijsen
    • , Carola Ammerlaan
    • , Ravian L. van Ineveld
    • , Sepide Derakhshan
    • , Sanne de Haan
    • , Emmy Dolman
    • , Philip Lijnzaad
    • , Lars Custers
    • , Harry Begthel
    • , Hindrik H. D. Kerstens
    • , Lindy L. Visser
    • , Maarten Rookmaaker
    • , Marianne Verhaar
    • , Godelieve A. M. Tytgat
    • , Patrick Kemmeren
    • , Ronald R. de Krijger
    • , Reem Al-Saadi
    • , Kathy Pritchard-Jones
    • , Marcel Kool
    • , Anne C. Rios
    • , Marry M. van den Heuvel-Eibrink
    • , Jan J. Molenaar
    • , Ruben van Boxtel
    • , Frank C. P. Holstege
    • , Hans Clevers
    •  & Jarno Drost
  • Article
    | Open Access

    PRDM14 is a critical transcription factor for mouse primordial germ cell specification, but its role in human remains unclear. Here, PRDM14 protein depletion using auxin-inducible degron uncovers a critical role for human germ cell specification, but regulation of a different set of target genes than in mouse.

    • Anastasiya Sybirna
    • , Walfred W. C. Tang
    • , Merrick Pierson Smela
    • , Sabine Dietmann
    • , Wolfram H. Gruhn
    • , Ran Brosh
    •  & M. Azim Surani
  • Article
    | Open Access

    hPSCs in culture acquire a more naïve pluripotent state upon tankyrase inhibition. Here, the authors show that tankyrase inhibitor-regulated naïve hiPSCs from diabetic donors generate more vascular progenitors and more efficient engraftment into mouse retina than conventional PSCs.

    • Tea Soon Park
    • , Ludovic Zimmerlin
    • , Rebecca Evans-Moses
    • , Justin Thomas
    • , Jeffrey S. Huo
    • , Riya Kanherkar
    • , Alice He
    • , Nensi Ruzgar
    • , Rhonda Grebe
    • , Imran Bhutto
    • , Michael Barbato
    • , Michael A. Koldobskiy
    • , Gerard Lutty
    •  & Elias T. Zambidis
  • Article
    | Open Access

    Clusters of enhancers, called super-enhancers (SEs), control the expression of cell identity genes. Here, the authors identify two types of enhancer units within SEs in ESCs, characterised by distinctive CpG methylation dynamics, and find that ESRRB regulates the enhancer units decommissioned at exit from naive pluripotency.

    • Emma Bell
    • , Edward W. Curry
    • , Wout Megchelenbrink
    • , Luc Jouneau
    • , Vincent Brochard
    • , Rute A. Tomaz
    • , King Hang T. Mau
    • , Yaser Atlasi
    • , Roshni A. de Souza
    • , Hendrik Marks
    • , Hendrik G. Stunnenberg
    • , Alice Jouneau
    •  & Véronique Azuara
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung spheroid cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung spheroid cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem cells.

    • Phuong-Uyen C. Dinh
    • , Dipti Paudel
    • , Hayden Brochu
    • , Kristen D. Popowski
    • , M. Cyndell Gracieux
    • , Jhon Cores
    • , Ke Huang
    • , M. Taylor Hensley
    • , Erin Harrell
    • , Adam C. Vandergriff
    • , Arianna K. George
    • , Raina T. Barrio
    • , Shiqi Hu
    • , Tyler A. Allen
    • , Kevin Blackburn
    • , Thomas G. Caranasos
    • , Xinxia Peng
    • , Lauren V. Schnabel
    • , Kenneth B. Adler
    • , Leonard J. Lobo
    • , Michael B. Goshe
    •  & Ke Cheng
  • Article
    | Open Access

    The role of the Klf5 in early and postnatal prostate development and in regeneration is unclear. Here, the authors show that Klf5 acetylation regulates and maintains luminal differentiation of prostate basal progenitors and is essential following androgen-induced regeneration.

    • Baotong Zhang
    • , Xinpei Ci
    • , Ran Tao
    • , Jianping Jenny Ni
    • , Xiaoyan Xuan
    • , Jamie L. King
    • , Siyuan Xia
    • , Yixiang Li
    • , Henry F. Frierson
    • , Dong-Kee Lee
    • , Jianming Xu
    • , Adeboye O. Osunkoya
    •  & Jin-Tang Dong
  • Article
    | Open Access

    Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

    • Anna S. E. Cuomo
    • , Daniel D. Seaton
    • , Davis J. McCarthy
    • , Iker Martinez
    • , Marc Jan Bonder
    • , Jose Garcia-Bernardo
    • , Shradha Amatya
    • , Pedro Madrigal
    • , Abigail Isaacson
    • , Florian Buettner
    • , Andrew Knights
    • , Kedar Nath Natarajan
    • , Chukwuma A. Agu
    • , Alex Alderton
    • , Petr Danecek
    • , Rachel Denton
    • , Richard Durbin
    • , Daniel J. Gaffney
    • , Angela Goncalves
    • , Reena Halai
    • , Sarah Harper
    • , Christopher M. Kirton
    • , Anja Kolb-Kokocinski
    • , Andreas Leha
    • , Shane A. McCarthy
    • , Yasin Memari
    • , Minal Patel
    • , Ewan Birney
    • , Francesco Paolo Casale
    • , Laura Clarke
    • , Peter W. Harrison
    • , Helena Kilpinen
    • , Ian Streeter
    • , Davide Denovi
    • , Ruta Meleckyte
    • , Natalie Moens
    • , Fiona M. Watt
    • , Willem H. Ouwehand
    • , Angus I. Lamond
    • , Dalila Bensaddek
    • , Philip Beales
    • , Ludovic Vallier
    • , John C. Marioni
    • , Mariya Chhatriwala
    •  & Oliver Stegle
  • Article
    | Open Access

    The signals regulating the establishment and maintenance of the pluripotent epiblast in human embryos are unclear. Here, the authors use a bioinformatics approach to identify the role of IGF1 in human embryo development, and from this, propose a culture medium with IGF1 together with Activin to sustain hESCs in the absence of FGF.

    • Sissy E. Wamaitha
    • , Katarzyna J. Grybel
    • , Gregorio Alanis-Lobato
    • , Claudia Gerri
    • , Sugako Ogushi
    • , Afshan McCarthy
    • , Shantha K. Mahadevaiah
    • , Lyn Healy
    • , Rebecca A. Lea
    • , Miriam Molina-Arcas
    • , Liani G. Devito
    • , Kay Elder
    • , Phil Snell
    • , Leila Christie
    • , Julian Downward
    • , James M. A. Turner
    •  & Kathy K. Niakan
  • Article
    | Open Access

    Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.

    • Xue Wang
    • , Haibo Xu
    • , Chaping Cheng
    • , Zhongzhong Ji
    • , Huifang Zhao
    • , Yaru Sheng
    • , Xiaoxia Li
    • , Jinming Wang
    • , Yu Shu
    • , Yuman He
    • , Liancheng Fan
    • , Baijun Dong
    • , Wei Xue
    • , Chee Wai Chua
    • , Dongdong Wu
    • , Wei-Qiang Gao
    •  & Helen He Zhu
  • Article
    | Open Access

    Myelosuppressive injuries lead to chronic MAPK activation and impair blood reconstitution. Here, the authors show that chronic activation endothelial MAPK impairs hematopoietic stem cell (HSC) function through NFkB signaling, and that post-myelosuppressive HSC defects can be reversed by administration of Stem Cell Growth Factor SCGFa.

    • Pradeep Ramalingam
    • , Michael G. Poulos
    • , Elisa Lazzari
    • , Michael C. Gutkin
    • , David Lopez
    • , Christopher C. Kloss
    • , Michael J. Crowley
    • , Lizabeth Katsnelson
    • , Ana G. Freire
    • , Matthew B. Greenblatt
    • , Christopher Y. Park
    •  & Jason M. Butler
  • Article
    | Open Access

    The identity of the earliest murine in vivo lung epithelial progenitors (marked by NKX2-1 expression) is unclear. Here, the authors use single-cell RNA sequencing to define the genetic program of these lung primordial progenitors, which will improve in vitro lung specification of pluripotent stem cells.

    • Laertis Ikonomou
    • , Michael J. Herriges
    • , Sara L. Lewandowski
    • , Robert Marsland III
    • , Carlos Villacorta-Martin
    • , Ignacio S. Caballero
    • , David B. Frank
    • , Reeti M. Sanghrajka
    • , Keri Dame
    • , Maciej M. Kańduła
    • , Julia Hicks-Berthet
    • , Matthew L. Lawton
    • , Constantina Christodoulou
    • , Attila J. Fabian
    • , Eric Kolaczyk
    • , Xaralabos Varelas
    • , Edward E. Morrisey
    • , John M. Shannon
    • , Pankaj Mehta
    •  & Darrell N. Kotton
  • Article
    | Open Access

    The molecular mechanisms regulating adult neural stem/progenitor cell differentiation following damage of the central nervous system are unclear. Here, the authors show that fibrinogen is a regulator of the adult neural stem/progenitor cell switch from neurogenesis to astrogenesis in a model of stroke

    • Lauriane Pous
    • , Sachin S. Deshpande
    • , Suvra Nath
    • , Szilvia Mezey
    • , Subash C. Malik
    • , Sebastian Schildge
    • , Christian Bohrer
    • , Könül Topp
    • , Dietmar Pfeifer
    • , Francisco Fernández-Klett
    • , Soroush Doostkam
    • , Dennis K. Galanakis
    • , Verdon Taylor
    • , Katerina Akassoglou
    •  & Christian Schachtrup
  • Article
    | Open Access

    The endothelial to haematopoietic transition (EHT) is the process where haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). Here the authors use single cell transcriptomics and antibody screening to identify CD44 as a marker of EHT that is required for EHT and HSPC development.

    • Morgan Oatley
    • , Özge Vargel Bölükbası
    • , Valentine Svensson
    • , Maya Shvartsman
    • , Kerstin Ganter
    • , Katharina Zirngibl
    • , Polina V. Pavlovich
    • , Vladislava Milchevskaya
    • , Vladimira Foteva
    • , Kedar N. Natarajan
    • , Bianka Baying
    • , Vladimir Benes
    • , Kiran R. Patil
    • , Sarah A. Teichmann
    •  & Christophe Lancrin
  • Article
    | Open Access

    Gut microbiota and their metabolites regulate homeostasis of the intestine, but their effects on intestine development are unclear. Here the authors use RNAseq and germ free mice to show that intestinal microbiota promote the expression of Erdr1, which increases Lgr5+ intestinal stem cell number and activity.

    • Hirohito Abo
    • , Benoit Chassaing
    • , Akihito Harusato
    • , Miguel Quiros
    • , Jennifer C. Brazil
    • , Vu L. Ngo
    • , Emilie Viennois
    • , Didier Merlin
    • , Andrew T. Gewirtz
    • , Asma Nusrat
    •  & Timothy L. Denning
  • Article
    | Open Access

    Neurogenesis is an ordered transition from pluriptotent cells to neural precursor cells (NPCs) to neurons. Here the authors show that loss of the lysine demethylases JMJD3 and UTX leads reduced DNA accessibility at neurogenesis loci in human NPCs, and that the chromatin remodeller BAF can rescue differentiation defects.

    • Yongli Shan
    • , Yanqi Zhang
    • , Yuan Zhao
    • , Tianyu Wang
    • , Jingyuan Zhang
    • , Jiao Yao
    • , Ning Ma
    • , Zechuan Liang
    • , Wenhao Huang
    • , Ke Huang
    • , Tian Zhang
    • , Zhenghui Su
    • , Qianyu Chen
    • , Yanling Zhu
    • , Chuman Wu
    • , Tiancheng Zhou
    • , Wei Sun
    • , Yanxing Wei
    • , Cong Zhang
    • , Chenxu Li
    • , Shuquan Su
    • , Baojian Liao
    • , Mei Zhong
    • , Xiaofen Zhong
    • , Jinfu Nie
    • , Duanqing Pei
    •  & Guangjin Pan
  • Article
    | Open Access

    Wnt signals for intestinal stem cell self-renewal originate from the stroma and Paneth cells, but the source in stomach is unclear. Here the authors identify a conserved population of stromal cells adjacent to stomach epithelia where Gli2 activates Wnt ligands to promote gastrointestinal regeneration and development.

    • Ji-Eun Kim
    • , Lijiang Fei
    • , Wen-Chi Yin
    • , Sabrina Coquenlorge
    • , Abilasha Rao-Bhatia
    • , Xiaoyun Zhang
    • , Sammy Shun Wai Shi
    • , Ju Hee Lee
    • , Noah A. Hahn
    • , Wasi Rizvi
    • , Kyoung-Han Kim
    • , Hoon-Ki Sung
    • , Chi-chung Hui
    • , Guoji Guo
    •  & Tae-Hee Kim