Stem cells

  • Article
    | Open Access

    Rap1 is a telomeric protein that is highly expressed in cancers. Here, the authors show that Rap1 interacts with several DNA repair proteins independent of its telomere function to enhance DNA repair and that its deficiency leads to accelerated tumorigenesis, but enhanced sensitivity to genotoxic stress.

    • Ekta Khattar
    • , Kyaw Ze Ya Maung
    • , Chen Li Chew
    • , Arkasubhra Ghosh
    • , Michelle Meng Huang Mok
    • , Pei Lee
    • , Jun Zhang
    • , Wei Hong Jeff Chor
    • , Gökhan Cildir
    • , Chelsia Qiuxia Wang
    • , Nur Khairiah Mohd-Ismail
    • , Desmond Wai Loon Chin
    • , Soo Chin Lee
    • , Henry Yang
    • , Yong-Jae Shin
    • , Do-Hyun Nam
    • , Liming Chen
    • , Alan Prem Kumar
    • , Lih Wen Deng
    • , Masahito Ikawa
    • , Jayantha Gunaratne
    • , Motomi Osato
    •  & Vinay Tergaonkar
  • Article
    | Open Access

    Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.

    • Giovanni Giuseppe Giobbe
    • , Claire Crowley
    • , Camilla Luni
    • , Sara Campinoti
    • , Moustafa Khedr
    • , Kai Kretzschmar
    • , Martina Maria De Santis
    • , Elisa Zambaiti
    • , Federica Michielin
    • , Laween Meran
    • , Qianjiang Hu
    • , Gijs van Son
    • , Luca Urbani
    • , Anna Manfredi
    • , Monica Giomo
    • , Simon Eaton
    • , Davide Cacchiarelli
    • , Vivian S. W. Li
    • , Hans Clevers
    • , Paola Bonfanti
    • , Nicola Elvassore
    •  & Paolo De Coppi
  • Article
    | Open Access

    XACT is a primate-specific TE-derived lncRNA that coats active X chromosomes in pluripotent cells and may contribute to species-specific regulation of X chromosome inactivation. Here, the authors investigate TEs associated with the XACT locus and identify a critical enhancer for its regulation, which evolved from an ancestral group of mammalian endogenous retroviruses, prior to the emergence of XACT.

    • Miguel Casanova
    • , Madeleine Moscatelli
    • , Louis Édouard Chauvière
    • , Christophe Huret
    • , Julia Samson
    • , Tharvesh Moideen Liyakat Ali
    • , Olga Rosspopoff
    •  & Claire Rougeulle
  • Article
    | Open Access

    Ageing is associated with clonal hematopoiesis of indeterminate potential (CHIP), which is linked to increased risks of hematological malignancies. Here the authors uncover an epigenetic mechanism through which mutant p53 drives clonal hematopoiesis through interaction with EZH2.

    • Sisi Chen
    • , Qiang Wang
    • , Hao Yu
    • , Maegan L. Capitano
    • , Sasidhar Vemula
    • , Sarah C. Nabinger
    • , Rui Gao
    • , Chonghua Yao
    • , Michihiro Kobayashi
    • , Zhuangzhuang Geng
    • , Aidan Fahey
    • , Danielle Henley
    • , Stephen Z. Liu
    • , Sergio Barajas
    • , Wenjie Cai
    • , Eric R. Wolf
    • , Baskar Ramdas
    • , Zhigang Cai
    • , Hongyu Gao
    • , Na Luo
    • , Yang Sun
    • , Terrence N. Wong
    • , Daniel C. Link
    • , Yunlong Liu
    • , H. Scott Boswell
    • , Lindsey D. Mayo
    • , Gang Huang
    • , Reuben Kapur
    • , Mervin C. Yoder
    • , Hal E. Broxmeyer
    • , Zhonghua Gao
    •  & Yan Liu
  • Article
    | Open Access

    Stem-cell-specific genes regulate processes such as maintenance, identity and/or division. Here, the authors show that in the Arabidopsis root TCX2, a gene expressed across different stem cell populations (a stem-cell-ubiquitous gene), controls division and identity by regulating stem-cell-type-specific networks.

    • Natalie M. Clark
    • , Eli Buckner
    • , Adam P. Fisher
    • , Emily C. Nelson
    • , Thomas T. Nguyen
    • , Abigail R. Simmons
    • , Maria A. de Luis Balaguer
    • , Tiara Butler-Smith
    • , Parnell J. Sheldon
    • , Dominique C. Bergmann
    • , Cranos M. Williams
    •  & Rossangela Sozzani
  • Article
    | Open Access

    How a precancerous form (dysplasia) becomes gastric cancer is unclear. Here, the authors assess the role of Kras activation in heterogenous dysplastic cells in murine stomach corpus organoids, identifying two dysplastic stem cell populations and show that MEK inhibition causes alterations in cell behavior.

    • Jimin Min
    • , Paige N. Vega
    • , Amy C. Engevik
    • , Janice A. Williams
    • , Qing Yang
    • , Loraine M. Patterson
    • , Alan J. Simmons
    • , R. Jarrett Bliton
    • , Joshua W. Betts
    • , Ken S. Lau
    • , Scott T. Magness
    • , James R. Goldenring
    •  & Eunyoung Choi
  • Article
    | Open Access

    The adult mammalian inner ear cells cannot regenerate nor proliferate. Here, the authors show that co-activation of Myc and NOTCH pathways can stimulate proliferation of inner ear sensory epithelial cells, which can be induced to become hair cell-like cells in vitro and in vivo.

    • Yilai Shu
    • , Wenyan Li
    • , Mingqian Huang
    • , Yi-Zhou Quan
    • , Deborah Scheffer
    • , Chunjie Tian
    • , Yong Tao
    • , Xuezhong Liu
    • , Konrad Hochedlinger
    • , Artur A. Indzhykulian
    • , Zhengmin Wang
    • , Huawei Li
    •  & Zheng-Yi Chen
  • Article
    | Open Access

    One of the underlying causes of aging is the accumulation of senescent cells, but their turnover rates and dynamics during ageing are unknown. Here the authors measure and model senescent cell production and removal and explore implications for mortality.

    • Omer Karin
    • , Amit Agrawal
    • , Ziv Porat
    • , Valery Krizhanovsky
    •  & Uri Alon
  • Article
    | Open Access

    How reproducible human kidney organoids derived from different iPSC lines are, and how faithful they are to human kidney tissue remain unclear. Here, the authors use four human iPSC lines to derive kidney organoids and show how organoid composition is reproducible, comparable to human tissue and of improved quality after transplantation.

    • Ayshwarya Subramanian
    • , Eriene-Heidi Sidhom
    • , Maheswarareddy Emani
    • , Katherine Vernon
    • , Nareh Sahakian
    • , Yiming Zhou
    • , Maria Kost-Alimova
    • , Michal Slyper
    • , Julia Waldman
    • , Danielle Dionne
    • , Lan T. Nguyen
    • , Astrid Weins
    • , Jamie L. Marshall
    • , Orit Rosenblatt-Rosen
    • , Aviv Regev
    •  & Anna Greka
  • Article
    | Open Access

    It remains unclear why quiescent neural stem cells (qNSCs) in the subventricular zone of the mouse brain have enlarged lysosomes. Here, authors demonstrate that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs, which prevents the NSC exit from quiescence.

    • Taeko Kobayashi
    • , Wenhui Piao
    • , Toshiya Takamura
    • , Hiroshi Kori
    • , Hitoshi Miyachi
    • , Satsuki Kitano
    • , Yumiko Iwamoto
    • , Mayumi Yamada
    • , Itaru Imayoshi
    • , Seiji Shioda
    • , Andrea Ballabio
    •  & Ryoichiro Kageyama
  • Article
    | Open Access

    Uterine gland development is essential for successful embryo implantation, decidua formation and placental development. Here the authors demonstrate that neonatal Wnt-dependent Lgr5 expressing stem/progenitor cells at the tips of developing glands are indispensable for uterine gland development.

    • Ryo Seishima
    • , Carly Leung
    • , Swathi Yada
    • , Katzrin Bte Ahmed Murad
    • , Liang Thing Tan
    • , Amin Hajamohideen
    • , Si Hui Tan
    • , Hideki Itoh
    • , Kazuhiro Murakami
    • , Yoshihiro Ishida
    • , Satoshi Nakamizo
    • , Yusuke Yoshikawa
    • , Esther Wong
    •  & Nick Barker
  • Article
    | Open Access

    Spermatogonial stem cells have the dual capacity to self-renew and differentiate into mature spermatozoa. Here, using transcriptome analyses of juvenile testes in gene-edited mice, the authors demonstrate that PRAMEF12 is required to maintain germ cell homeostasis and promote their differentiation.

    • Zhengpin Wang
    • , Xiaojiang Xu
    • , Jian-Liang Li
    • , Cameron Palmer
    • , Dragan Maric
    •  & Jurrien Dean
  • Article
    | Open Access

    LncRNA loci potentially contain multiple modes that can exert function, including DNA regulatory elements. Here, the authors generated genetic models in mice to dissect the role of the syntenically conserved lncRNA Firre in the context of hematopoiesis.

    • Jordan P. Lewandowski
    • , James C. Lee
    • , Taeyoung Hwang
    • , Hongjae Sunwoo
    • , Jill M. Goldstein
    • , Abigail F. Groff
    • , Nydia P. Chang
    • , William Mallard
    • , Adam Williams
    • , Jorge Henao-Meija
    • , Richard A. Flavell
    • , Jeannie T. Lee
    • , Chiara Gerhardinger
    • , Amy J. Wagers
    •  & John L. Rinn
  • Article
    | Open Access

    C. elegans is a commonly used model organism in the study of ageing, and differences in genetic background can result in varying strain longevity. Here the authors demonstrate that a background mutation in fln-2 affects life-limiting pharyngeal infection and that in the mutant background the beneficial effect of sir-2.1 over-expression is suppressed.

    • Yuan Zhao
    • , Hongyuan Wang
    • , Richard J. Poole
    •  & David Gems
  • Article
    | Open Access

    Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression

    • Iuliia O. Peshkova
    • , Turan Aghayev
    • , Aliia R. Fatkhullina
    • , Petr Makhov
    • , Elizaveta K. Titerina
    • , Satoru Eguchi
    • , Yin Fei Tan
    • , Andrew V. Kossenkov
    • , Marina V. Khoreva
    • , Lyudmila V. Gankovskaya
    • , Stephen M. Sykes
    •  & Ekaterina K. Koltsova
  • Article
    | Open Access

    Currently, few mouse models exist to recapitulate human melanomagenesis. Here, the authors establish a c-Kit-CreER-driven model to target melanocyte stem cells (McSCs) and show that oncogenic McSCs give rise to epidermal melanoma that invade into the dermis, similar to human melanoma.

    • Qi Sun
    • , Wendy Lee
    • , Yasuaki Mohri
    • , Makoto Takeo
    • , Chae Ho Lim
    • , Xiaowei Xu
    • , Peggy Myung
    • , Radhika P. Atit
    • , M. Mark Taketo
    • , Rana S. Moubarak
    • , Markus Schober
    • , Iman Osman
    • , Denise L. Gay
    • , Dieter Saur
    • , Emi K. Nishimura
    •  & Mayumi Ito
  • Article
    | Open Access

    The development of post-chemotherapy resistance is a significant issue in the management of AML. Here, Caiado et al. suggest that the issue might be circumvented via upfront combination with hypomethylating agents that shape the clonal dynamics and transcriptional landscape of relapsing AML

    • Francisco Caiado
    • , Diogo Maia-Silva
    • , Carolina Jardim
    • , Nina Schmolka
    • , Tânia Carvalho
    • , Cláudia Reforço
    • , Rita Faria
    • , Branka Kolundzija
    • , André E. Simões
    • , Tuncay Baubec
    • , Christopher R. Vakoc
    • , Maria Gomes da Silva
    • , Markus G. Manz
    • , Ton N. Schumacher
    • , Håkan Norell
    •  & Bruno Silva-Santos
  • Article
    | Open Access

    In breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation

    • Rachel Eyre
    • , Denis G. Alférez
    • , Angélica Santiago-Gómez
    • , Kath Spence
    • , James C. McConnell
    • , Claire Hart
    • , Bruno M. Simões
    • , Diane Lefley
    • , Claudia Tulotta
    • , Joanna Storer
    • , Austin Gurney
    • , Noel Clarke
    • , Mick Brown
    • , Sacha J. Howell
    • , Andrew H. Sims
    • , Gillian Farnie
    • , Penelope D. Ottewell
    •  & Robert B. Clarke
  • Article
    | Open Access

    The ovary is covered by a surface epithelium (OSE) and cells mediating its repair post ovulation are unclear. Here, the authors identify the Protein C Receptor (Procr) as marking progenitor cells, distinct from Lgr5+ stem cells, on the murine surface epithelium that repair the OSE post ovulation.

    • Jingqiang Wang
    • , Daisong Wang
    • , Kun Chu
    • , Wen Li
    •  & Yi Arial Zeng
  • Article
    | Open Access

    Hydralazine is a drug used in the treatment of heart failure and cancer, and it has recently been shown to promote lifespan in C. elegans. Here, the authors elucidate the mechanism of action of hydralazine, and show that it targets PKA to promote mitochondrial function via Sirtuin1/5.

    • Esmaeil Dehghan
    • , Mohammad Goodarzi
    • , Bahar Saremi
    • , Rueyling Lin
    •  & Hamid Mirzaei
  • Article
    | Open Access

    Decreased autophagy is a hallmark of ageing, but its inter-tissue regulation is poorly understood. Here, Zhou et al. identify mir-83 in C. elegans, which is transported across tissues and suppresses autophagy, contributing to age-related decline.

    • Yifei Zhou
    • , Xueqing Wang
    • , Mengjiao Song
    • , Zhidong He
    • , Guizhong Cui
    • , Guangdun Peng
    • , Christoph Dieterich
    • , Adam Antebi
    • , Naihe Jing
    •  & Yidong Shen
  • Article
    | Open Access

    Trophectoderm lineage development is essential for implantation, placentation, and healthy pregnancy. Here the authors map super-enhancers (SEs) in trophoblast stem cells and find both TE-specific master regulators and 150 previous uncharacterised transcription factors that are SE-associated, providing insight into trophectoderm-specific regulatory networks.

    • Bum-Kyu Lee
    • , Yu jin Jang
    • , Mijeong Kim
    • , Lucy LeBlanc
    • , Catherine Rhee
    • , Jiwoon Lee
    • , Samuel Beck
    • , Wenwen Shen
    •  & Jonghwan Kim
  • Article
    | Open Access

    Previous gene editing in haematopoietic stem cells (HSCs) has focussed on a heterogeneous CD34+ population. Here, the authors demonstrate high efficiency CRISPR/Cas9-based editing of purified long-term HSCs using non-homologous end joining and homology-directed repair, by directing isoform-specific expression of GATA1.

    • Elvin Wagenblast
    • , Maria Azkanaz
    • , Sabrina A. Smith
    • , Lorien Shakib
    • , Jessica L. McLeod
    • , Gabriela Krivdova
    • , Joana Araújo
    • , Leonard D. Shultz
    • , Olga I. Gan
    • , John E. Dick
    •  & Eric R. Lechman
  • Article
    | Open Access

    Pluripotent stem cell colonies are encircled by large cornerstone focal adhesions (FAs). Here, using super-resolution imaging, the authors describe features in the nanoscale makeup of these stable FAs such as inverted vinculin, lateral talin segregation and distinct kank protein distributions.

    • Aki Stubb
    • , Camilo Guzmán
    • , Elisa Närvä
    • , Jesse Aaron
    • , Teng-Leong Chew
    • , Markku Saari
    • , Mitro Miihkinen
    • , Guillaume Jacquemet
    •  & Johanna Ivaska
  • Article
    | Open Access

    Telomere shortening is associated with aging. Here the authors analyze mice with hyperlong telomeres and demonstrate that longer telomeres than normal have beneficial effects such as delayed metabolic aging, increased longevity and less incidence of cancer.

    • Miguel A. Muñoz-Lorente
    • , Alba C. Cano-Martin
    •  & Maria A. Blasco
  • Article
    | Open Access

    Mosaic loss of chromosome Y (mLOY) is associated with age and smoking but also genetic factors play a role. Here, Terao et al. perform GWAS for mLOY in 95,380 Japanese men and identify 46 loci that overlap with hematopoietic stem cell enhancers and transcription factor binding sites critical for hematopoiesis.

    • Chikashi Terao
    • , Yukihide Momozawa
    • , Kazuyoshi Ishigaki
    • , Eiryo Kawakami
    • , Masato Akiyama
    • , Po-Ru Loh
    • , Giulio Genovese
    • , Hiroki Sugishita
    • , Tazro Ohta
    • , Makoto Hirata
    • , John R. B. Perry
    • , Koichi Matsuda
    • , Yoshinori Murakami
    • , Michiaki Kubo
    •  & Yoichiro Kamatani
  • Article
    | Open Access

    Epidermal homeostasis requires long term stem cell function. Here, the authors apply transcriptional circuitry analysis based on integrated epigenomic profiling of primary human keratinocytes with high and low stem cell function to identify IRF2 as a negative regulator of stemness.

    • Nicolas Mercado
    • , Gabi Schutzius
    • , Christian Kolter
    • , David Estoppey
    • , Sebastian Bergling
    • , Guglielmo Roma
    • , Caroline Gubser Keller
    • , Florian Nigsch
    • , Adrian Salathe
    • , Remi Terranova
    • , John Reece-Hoyes
    • , John Alford
    • , Carsten Russ
    • , Judith Knehr
    • , Dominic Hoepfner
    • , Alexandra Aebi
    • , Heinz Ruffner
    • , Tanner C. Beck
    • , Sajjeev Jagannathan
    • , Calla M. Olson
    • , Hadley E. Sheppard
    • , Selma Z. Elsarrag
    • , Tewis Bouwmeester
    • , Mathias Frederiksen
    • , Felix Lohmann
    • , Charles Y. Lin
    •  & Susan Kirkland
  • Article
    | Open Access

    Dynamic mesenchyme derived signals are known to direct proper organ formation and cell specification in vivo. Here the authors show in mice that mesenchyme derived Hedgehog and Wnt instruct the formation of the pancreas and beta cells, and that Wnt inhibition promotes beta cell formation from human pluripotent cells.

    • Theodora Yung
    • , Frankie Poon
    • , Minggao Liang
    • , Sabrina Coquenlorge
    • , Emily C. McGaugh
    • , Chi-chung Hui
    • , Michael D. Wilson
    • , M. Cristina Nostro
    •  & Tae-Hee Kim
  • Article
    | Open Access

    A challenge in cell therapy for photoreceptor degeneration is inducing the grafted cells to grow and maintain light sensitive outer segments. Here, the authors use optogenetics to circumvent this problem and restore visual function in blind mice.

    • Marcela Garita-Hernandez
    • , Maruša Lampič
    • , Antoine Chaffiol
    • , Laure Guibbal
    • , Fiona Routet
    • , Tiago Santos-Ferreira
    • , Sylvia Gasparini
    • , Oliver Borsch
    • , Giuliana Gagliardi
    • , Sacha Reichman
    • , Serge Picaud
    • , José-Alain Sahel
    • , Olivier Goureau
    • , Marius Ader
    • , Deniz Dalkara
    •  & Jens Duebel
  • Article
    | Open Access

    Vectors used in gene therapy for hemoglobin disorders carry globin in a reverse-orientation to prevent the loss of key regulatory elements by RNA splicing, but this limits their efficiency. Here, the authors develop a vector carrying β-globin in a forward orientation and show that it has improved titers and transduction efficiency in humanized mice and nonhuman primates.

    • Naoya Uchida
    • , Matthew M. Hsieh
    • , Lydia Raines
    • , Juan J. Haro-Mora
    • , Selami Demirci
    • , Aylin C. Bonifacino
    • , Allen E. Krouse
    • , Mark E. Metzger
    • , Robert E. Donahue
    •  & John F. Tisdale
  • Article
    | Open Access

    Barriers underlying the inefficiency of reprogramming cells to pluripotency are poorly defined. Here the authors identify a transient interval soon after pluripotency exit that permits high-efficiency reprogramming and is facilitated by OCT4 bound elements displaying unique silencing behaviour during differentiation.

    • Sudhir Thakurela
    • , Camille Sindhu
    • , Evgeny Yurkovsky
    • , Christina Riemenschneider
    • , Zachary D. Smith
    • , Iftach Nachman
    •  & Alexander Meissner
  • Article
    | Open Access

    In regenerative animals, how cells respond to injury signals inducing senescence is unclear. Here, the authors show that cells from highly regenerative mammals are resistant to ROS-induced cellular senescence, but non-regenerating species exhibit mitochondrial dysfunction/senescence in response to hydrogen peroxide exposure.

    • Sandeep Saxena
    • , Hemendra Vekaria
    • , Patrick G. Sullivan
    •  & Ashley W. Seifert
  • Article
    | Open Access

    The biology of the urothelium has been difficult to study given the lack of methods to propagate these cells. Here, the authors generate mouse urothelial organoids derived from bladder urothelial cells with high CD49f/ITGA6 and define what regulates urothelium differentiation, which is PPARγ, EGFR and Notch signalling.

    • Catarina P. Santos
    • , Eleonora Lapi
    • , Jaime Martínez de Villarreal
    • , Laura Álvaro-Espinosa
    • , Asunción Fernández-Barral
    • , Antonio Barbáchano
    • , Orlando Domínguez
    • , Ashley M. Laughney
    • , Diego Megías
    • , Alberto Muñoz
    •  & Francisco X. Real
  • Article
    | Open Access

    Epithelial turnover in the colon requires stem cells in the crypt that express the R-spondin receptor Lgr5. Here, the authors show that regeneration after colon injury involving loss of Lgr5+ and Axin2+ cells requires stromal derived Rspo3-dependent reprogramming of Lgr4+ differentiated cells, including Krt20+ enterocytes.

    • Christine Harnack
    • , Hilmar Berger
    • , Agne Antanaviciute
    • , Ramon Vidal
    • , Sascha Sauer
    • , Alison Simmons
    • , Thomas F. Meyer
    •  & Michael Sigal
  • Article
    | Open Access

    Age-related tissue alterations have been associated with a decline in stem cell number and function. Here the authors report a single cell multi-omics study of mouse muscle stem cells, combining single cell transcriptome and DNA methylome profiling and find that aged cells have a global increase of uncoordinated transcriptional heterogeneity biased towards genes regulating cell-niche interactions.

    • Irene Hernando-Herraez
    • , Brendan Evano
    • , Thomas Stubbs
    • , Pierre-Henri Commere
    • , Marc Jan Bonder
    • , Stephen Clark
    • , Simon Andrews
    • , Shahragim Tajbakhsh
    •  & Wolf Reik
  • Article
    | Open Access

    Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here the authors show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.

    • Romina Aron Badin
    • , Aurore Bugi
    • , Susannah Williams
    • , Marta Vadori
    • , Marie Michael
    • , Caroline Jan
    • , Alberto Nassi
    • , Sophie Lecourtois
    • , Antoine Blancher
    • , Emanuele Cozzi
    • , Philippe Hantraye
    •  & Anselme L. Perrier
  • Article
    | Open Access

    Epithelia are exposed to diverse types of environmental stress, but the mechanisms by which epithelial cells sense stress are not well understood. Here, the authors show that a Nox-ROS-Ask1-MKK3-p38 signaling axis integrates various types of stress to promote intestinal regeneration.

    • Parthive H. Patel
    • , Clothilde Pénalva
    • , Michael Kardorff
    • , Marianne Roca
    • , Bojana Pavlović
    • , Anja Thiel
    • , Aurelio A. Teleman
    •  & Bruce A. Edgar
  • Article
    | Open Access

    There is a lack of human models to study vocal fold epithelia making it difficult to provide therapies for vocal fold disease. Here, the authors generate a human-based model of vocal fold mucosa that mimics in utero development and shows inflammation on exposure to cigarette smoke abstract.

    • Vlasta Lungova
    • , Xia Chen
    • , Ziyue Wang
    • , Christina Kendziorski
    •  & Susan L. Thibeault
  • Article
    | Open Access

    Cardiomyocytes obtained from human induced pluripotent stem cells are increasingly used for drug testing, but they are not always predictive of the heart contractile responses. Here the authors develop a method to measure cytosolic calcium, action potentials and contraction simultaneously, to achieve higher sensitivity for drug screenings.

    • Berend J. van Meer
    • , Ana Krotenberg
    • , Luca Sala
    • , Richard P. Davis
    • , Thomas Eschenhagen
    • , Chris Denning
    • , Leon G. J. Tertoolen
    •  & Christine L. Mummery
  • Article
    | Open Access

    TRIM66 protein has an N-terminal tripartite motif and a C-terminal PHD Bromodomain. Here the authors show the specific histone modification recognition of TRIM66-PHD-Bromodomain through crystallography and biochemistry assay, and further reveal that TRIM66 recognition of certain histone modification is important for DNA damage repair in ESCs.

    • Jiajing Chen
    • , Zikang Wang
    • , Xudong Guo
    • , Fudong Li
    • , Qingtao Wei
    • , Xuwen Chen
    • , Deshun Gong
    • , Yanxin Xu
    • , Wen Chen
    • , Yongrui Liu
    • , Jiuhong Kang
    •  & Yunyu Shi
  • Article
    | Open Access

    PAX7 transcription factor specifies the myogenic identity of muscle stem cells and acts as a nodal factor by stimulating proliferation while inhibiting differentiation. Here authors find that Mll1 deletion in myoblasts in mice results in reduced H3K4me3 at both Pax7 and Myf5 promoters, reduced Pax7 and Myf5 expression, and proliferation defects.

    • Gregory C. Addicks
    • , Caroline E. Brun
    • , Marie-Claude Sincennes
    • , John Saber
    • , Christopher J. Porter
    • , A. Francis Stewart
    • , Patricia Ernst
    •  & Michael A. Rudnicki
  • Article
    | Open Access

    Maintenance of high turnover in tissues such as epidermis requires balance between proliferation and differentiation. Here the authors show that HNRNPK promotes RNA Polymerase II binding to proliferation and self-renewal genes as well as degradation of differentiation promoting mRNAs together with DDX6 in epidermis.

    • Jingting Li
    • , Yifang Chen
    • , Xiaojun Xu
    • , Jackson Jones
    • , Manisha Tiwari
    • , Ji Ling
    • , Ying Wang
    • , Olivier Harismendy
    •  & George L. Sen
  • Article
    | Open Access

    Notch signaling mediates intestinal enteroblast specification in Drosophila but the molecular mechanism as to how this is regulated is unclear. Here, the authors show that the transcription factor Klumpfuss ensures enteroblast commitment through repression of enteroendocrine cell fate downstream of Notch.

    • Jerome Korzelius
    • , Sina Azami
    • , Tal Ronnen-Oron
    • , Philipp Koch
    • , Maik Baldauf
    • , Elke Meier
    • , Imilce A. Rodriguez-Fernandez
    • , Marco Groth
    • , Pedro Sousa-Victor
    •  & Heinrich Jasper
  • Article
    | Open Access

    Per-O-acetylated unnatural monosaccharides are popular tools for glycan labeling in live cells but can undergo unwanted side reactions with cysteines. Here, the authors develop unnatural sugars in a partially esterified form that are inert towards cysteines, and use them to probe O-GlcNAcylation in mESCs.

    • Yi Hao
    • , Xinqi Fan
    • , Yujie Shi
    • , Che Zhang
    • , De-en Sun
    • , Ke Qin
    • , Wei Qin
    • , Wen Zhou
    •  & Xing Chen
  • Article
    | Open Access

    Wounding induces changes in cell identity but the mechanisms regulating this are unclear. Here, the authors show that Sox11/Sox4 expression in the leading edge of wounds converts murine epidermal cells to an embryonic-like state and facilitates repair.

    • Qi Miao
    • , Matthew C. Hill
    • , Fengju Chen
    • , Qianxing Mo
    • , Amy T. Ku
    • , Carlos Ramos
    • , Elisabeth Sock
    • , Véronique Lefebvre
    •  & Hoang Nguyen
  • Article
    | Open Access

    The EWS-ATF1 fusion gene causes clear cell sarcoma (CCS). Here, the authors show that the downstream effects of EWS-ATF1 expression are strictly context dependent, and reveal the cell of origin for CCS to be Tppp3-expressing cells in peripheral nerves.

    • Shingo Komura
    • , Kenji Ito
    • , Sho Ohta
    • , Tomoyo Ukai
    • , Mio Kabata
    • , Fumiaki Itakura
    • , Katsunori Semi
    • , Yutaka Matsuda
    • , Kyoichi Hashimoto
    • , Hirofumi Shibata
    • , Masamitsu Sone
    • , Norihide Jo
    • , Kazuya Sekiguchi
    • , Takatoshi Ohno
    • , Haruhiko Akiyama
    • , Katsuji Shimizu
    • , Knut Woltjen
    • , Manabu Ozawa
    • , Junya Toguchida
    • , Takuya Yamamoto
    •  & Yasuhiro Yamada
  • Article
    | Open Access

    Noise due to genetic heterogeneity potentially impacts the the discovery of genes that contribute to diseases such as schizophrenia (SCZ). In this study, authors minimize the disease-irrelevant noise between SCZ and healthy individuals by profiling transcriptional signatures among discordant monozygotic twin pairs, and demonstrate that although sexes share many of the final common pathways, the underlying primary pathophysiology of SCZ differs between males and females.

    • Jari Tiihonen
    • , Marja Koskuvi
    • , Markus Storvik
    • , Ida Hyötyläinen
    • , Yanyan Gao
    • , Katja A. Puttonen
    • , Raisa Giniatullina
    • , Ekaterina Poguzhelskaya
    • , Ilkka Ojansuu
    • , Olli Vaurio
    • , Tyrone D. Cannon
    • , Jouko Lönnqvist
    • , Sebastian Therman
    • , Jaana Suvisaari
    • , Jaakko Kaprio
    • , Lesley Cheng
    • , Andrew F. Hill
    • , Markku Lähteenvuo
    • , Jussi Tohka
    • , Rashid Giniatullin
    • , Šárka Lehtonen
    •  & Jari Koistinaho
  • Article
    | Open Access

    Use of Assisted Reproductive Technologies (ART) is increasing globally but their impact on long term health remains unclear. Here the authors show that ART-conceived individuals show variation in epigenetic profile at birth that largely resolves by adulthood, with no evidence of an impact on long term outcomes.

    • Boris Novakovic
    • , Sharon Lewis
    • , Jane Halliday
    • , Joanne Kennedy
    • , David P. Burgner
    • , Anna Czajko
    • , Bowon Kim
    • , Alexandra Sexton-Oates
    • , Markus Juonala
    • , Karin Hammarberg
    • , David J. Amor
    • , Lex W. Doyle
    • , Sarath Ranganathan
    • , Liam Welsh
    • , Michael Cheung
    • , John McBain
    • , Robert McLachlan
    •  & Richard Saffery
  • Article
    | Open Access

    The T-box protein TBR2 is involved in cortical neurogenesis expansion during neurodevelopment and is preferentially enriched in intermediate progenitors. The authors show that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly in the mouse cortex via PCDH19.

    • Xiaohui Lv
    • , Si-Qiang Ren
    • , Xin-Jun Zhang
    • , Zhongfu Shen
    • , Tanay Ghosh
    • , Anjin Xianyu
    • , Peng Gao
    • , Zhizhong Li
    • , Susan Lin
    • , Yang Yu
    • , Qiangqiang Zhang
    • , Matthias Groszer
    •  & Song-Hai Shi
  • Article
    | Open Access

    Hair follicles (HFs) are sensitive to chemotherapy but recover from quiescent HF stem cells, although sometimes chemotherapy results in permanent loss. Here, Kim et al. establish a model of permanent chemotherapy-induced alopecia to uncover the underlying mechanisms depleting human HF stem cells.

    • Jin Yong Kim
    • , Jungyoon Ohn
    • , Ji-Seon Yoon
    • , Bo Mi Kang
    • , Minji Park
    • , Sookyung Kim
    • , Woochan Lee
    • , Sungjoo Hwang
    • , Jong-Il Kim
    • , Kyu Han Kim
    •  & Ohsang Kwon