Stem cells

  • 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
    •  & 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
    •  & 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
    •  & Fredrik Lanner
  • 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
    •  & 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
    •  & 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
    •  & Ramiro Iglesias-Bartolome
  • 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
    •  & 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
    •  & 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
    •  & Catherine M. Verfaillie
  • 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
    •  & 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
    •  & 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
    •  & 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
    •  & Ke Cheng
  • 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & Tae-Hee Kim
  • Article
    | Open Access

    Besides its role in splicing, U1 snRNP can suppress pre-mRNA cleavage and polyadenylation. The authors show that the nuclear cap-binding complex component Srrt/Ars2 maintains embryonic stem cell identity by promoting U1 recruitment to first introns and preventing premature termination of multiple transcripts.

    • Yaroslav A. Kainov
    •  & Eugene V. Makeyev
  • Article
    | Open Access

    Bone marrow stromal cells (BMSCs) lining sinusoidal blood vessels are mesenchymal cells whose function is critical for the skeleton. Here the authors show that quiescent CXCL12-expressing BMSCs can convert into a skeletal stem cell-like state, and differentiate into cortical bone osteoblasts only in response to injury.

    • Yuki Matsushita
    • , Mizuki Nagata
    •  & Noriaki Ono
  • Article
    | Open Access

    Human induced pluripotent stem cell-derived intestinal organoids (HIOs) are powerful tools to study development and diseases of the gastrointestinal tract. Here, the authors develop a directed differentiation protocol to generate mesenchyme-free HIOs that can be patterned towards proximal small intestine or colonic epithelium, and demonstrated their utility in modeling CFTR function.

    • Aditya Mithal
    • , Amalia Capilla
    •  & Gustavo Mostoslavsky
  • Article
    | Open Access

    Point mutations have been found in induced pluripotent stem cells (iPSCs) but when they arise is unclear. Here, the authors show that a G1/S cell cycle checkpoint deficiency transiently occurs early in genome reprogramming, suggesting a common developmental pathway between iPSC and tumorigenesis, and generate genetic burden-free human iPSCs.

    • Ryoko Araki
    • , Yuko Hoki
    •  & Masumi Abe
  • Article
    | Open Access

    Acetylcholine regulates intestinal epithelial secretion via muscarinic Gq-coupled receptors but its role in cell differentiation is unclear. Here, the authors show that Prox1-positive endocrine cells are sensors for the cholinergic intestinal niche and can trigger increased differentiation of enteroendocrine DCLK1-positive tuft cells.

    • Moritz Middelhoff
    • , Henrik Nienhüser
    •  & Timothy C. Wang
  • Article
    | Open Access

    The cellular composition of previous engineered heart tissue is often heterogeneous. Here, the authors create chamber-specific human pluripotent stem cell-derived cardiomyocytes to form both ventricular and atrial cells before embedding in collagen-based matrix to form ring-shaped engineered heart tissue.

    • Idit Goldfracht
    • , Stephanie Protze
    •  & Lior Gepstein
  • Article
    | Open Access

    Cancers arising from the gastric squamous-columnar junction have high incidence and are characterized by a poor prognosis. Here, the authors use genetic mouse models to show that loss of p53 and Rb1 expression results in preferential tumour development at the gastric squamous-columnar junction that contains a large pool of osteopontin responsive Lgr5-CD44+ cells.

    • Dah-Jiun Fu
    • , Lianghai Wang
    •  & Alexander Yu. Nikitin
  • Article
    | Open Access

    Sertoli cells and other somatic cells of the testis comprise the germ cell niche and are critical to regulate spermatogenesis. Here the authors present a method in which Sertoli cells are selectively targeted for ablation by the compound benzalkonium chloride (BC) in mice, and the spermatogenic niche is subsequently repopulated in regions that have been affected by BC treatment.

    • Tetsuhiro Yokonishi
    • , Jennifer McKey
    •  & Blanche Capel
  • Article
    | Open Access

    Intestinal aging is associated with declines in structure and absorption of nutrients. Here, the authors show that aging related intestinal decline is mediated by activation of the mTORC1-p38MAPK-p53 pathway in intestinal stem cells and can be ameliorated by abrogating mTORC1 or p38MAPK activity.

    • Dan He
    • , Hongguang Wu
    •  & Baojie Li
  • Article
    | Open Access

    Skeletal muscle stem cells express the transcription factor Pax7. Here, the authors isolate, from human muscle, cells that are positive for the endothelial marker CLEC14A and show that despite not expressing pax7, these cells regenerate muscle and contribute to the muscle stem cell niche when transplanted into mice.

    • Andreas Marg
    • , Helena Escobar
    •  & Simone Spuler
  • 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
    •  & Paolo De Coppi
  • 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
    •  & Yan Liu
  • 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
    •  & Claire Rougeulle
  • 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
    •  & Rossangela Sozzani
  • 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
    •  & Ryoichiro Kageyama
  • 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
    •  & Anna Greka
  • 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
    •  & Nick Barker
  • 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
    •  & John L. Rinn
  • 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
    •  & Ekaterina K. Koltsova