Stem cells

  • Article
    | Open Access

    Here the authors identify PHF3 SPOC domain as a reader of the phosphorylated RNA polymerase II (Pol II) C-terminal domain. They show that PHF3 clusters with Pol II complexes in cells, drives phase separation of Pol II in vitro, and regulates neuronal gene expression and neuronal differentiation.

    • Lisa-Marie Appel
    • , Vedran Franke
    •  & Dea Slade
  • Article
    | Open Access

    Biomechanical mechanisms orchestrating stem cell dynamics in development remain unclear. Here the authors show that guidance receptor Plexin-B2 organizes actomyosin contractility, cytoskeletal tension and adhesion during multicellular development of human embryonic stem cells and neuroprogenitor cells.

    • Chrystian Junqueira Alves
    • , Rafael Dariolli
    •  & Roland H. Friedel
  • Article
    | Open Access

    The connection between cell cycle, metabolic state and mitochondrial activity is unclear. Here, the authors show that p107 represses mitochondrial transcription and ATP output in response to glycolytic byproducts, causing metabolic control of the cell cycle rate in myogenic progenitors.

    • Debasmita Bhattacharya
    • , Vicky Shah
    •  & Anthony Scimè
  • Article
    | Open Access

    A localized Wnt3a signal has been shown to induce asymmetric division of mouse embryonic stem cells. Here the authors develop SET-seq, an approach to jointly profile epigenome and transcriptome in the same single cell and use it to provide mechanistic insights into the gene regulatory programs for maintaining and resetting stem cell fate during differentiation.

    • Zhongxing Sun
    • , Yin Tang
    •  & Dong Fang
  • Article
    | Open Access

    A comprehensive analysis of the ocular networks among various tissues is necessary to understand eye physiology in health and disease. Here the authors present a multi-species single-cell transcriptomic atlas consisting of cells of the cornea, iris, ciliary body, neural retina, retinal pigmented epithelium, and choroid.

    • Pradeep Gautam
    • , Kiyofumi Hamashima
    •  & Yuin-Han Loh
  • Article
    | Open Access

    KLF4, OCT4, SOX2 and MYC cooperate to reorganize chromatin during somatic cell reprogramming. Here the authors show that KLF4 forms a liquid-like biomolecular condensate that recruits OCT4 and SOX2, and that condensation of the isolated KLF4 DNA binding domain with DNA is enhanced by CpG methylation

    • Rajesh Sharma
    • , Kyoung-Jae Choi
    •  & Josephine C. Ferreon
  • Article
    | Open Access

    Human early development remains largely inaccessible, owing to technical and ethical limitations of working with natural embryos. Here the authors assess the extent to which human expanded pluripotent stem cells can specify distinct cell lineages and capture aspects of early human embryogenesis.

    • Berna Sozen
    • , Victoria Jorgensen
    •  & Magdalena Zernicka-Goetz
  • Article
    | Open Access

    Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Here the authors generate mutant clonal intestinal organoids for 19 host genes previously implicated in coronavirus biology and identify the cell surface protease TMPRSS2 as a potential therapeutic target.

    • Joep Beumer
    • , Maarten H. Geurts
    •  & Hans Clevers
  • Article
    | Open Access

    Polycomb repressive complexes (PRC1 and PRC2) repress genes that are crucial for development via epigenetic modifications; however, their role in differentiation is not well known. Here the authors reveal that a PCGF1-containing PRC1 variant facilitates exit from pluripotency by downregulating target genes and recruiting PRC2.

    • Hiroki Sugishita
    • , Takashi Kondo
    •  & Haruhiko Koseki
  • Article
    | Open Access

    Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.

    • Kellen Chen
    • , Sun Hyung Kwon
    •  & Geoffrey C. Gurtner
  • Article
    | Open Access

    Mutations in CNTNAP2 have been associated with a syndromic form of Autism Spectrum Disorder. Here the authors show that forebrain organoids generated from induced pluripotent stem cells of patients with a syndromic form of ASD with a homozygous truncating mutation in CNTNAP2 displayed an increase in volume and total cell number, which is driven by abnormal cellular proliferation and neurogenesis.

    • Job O. de Jong
    • , Ceyda Llapashtica
    •  & Sander Markx
  • Article
    | Open Access

    Previous approaches to derive embryoids either lack physiological morphology and signaling interactions, or are unconducive to model post-gastrulation development. Here the authors use a high-throughput approach to induce mouse embryonic stem cells into epiblast-like aggregates, which are then co-cultured with mouse trophoblast stem cell aggregates, to yield embryoids with axial morphogenesis and anterior development.

    • Mehmet U. Girgin
    • , Nicolas Broguiere
    •  & Matthias P. Lutolf
  • Article
    | Open Access

    Although the interactors of pluripotency factors have been identified in mouse embryonic stem cells (ESCs), their interactors in human ESCs remain unexplored. Here the authors map OCT4 protein interactions in naïve and primed human ESCs to find specific interactions with BAF subunits that promote an open chromatin architecture at blastocyst-associated genes and ectodermal genes, respectively.

    • Xin Huang
    • , Kyoung-mi Park
    •  & Thorold W. Theunissen
  • Article
    | Open Access

    There is a pressing need to develop representative organ-like platforms recapitulating complex in vivo phenotypes to study human development and disease in vitro. Here the authors present a method to generate human heart organoids by self-assembly using pluripotent stem cells, compare these to age-matched fetal cardiac tissues and recreate a model of pregestational diabetes.

    • Yonatan R. Lewis-Israeli
    • , Aaron H. Wasserman
    •  & Aitor Aguirre
  • Article
    | Open Access

    Human and murine embryonic development has disparities, highlighting the need for primate systems. Here, the authors construct a post-implantation transcriptional atlas from non-human primate embryos and show ISL1 controls a gene regulatory network in the amnion required for mesoderm formation.

    • Ran Yang
    • , Alexander Goedel
    •  & Kenneth R. Chien
  • Article
    | Open Access

    Cells in the developing embryo interpret WNT signalling with context-dependence, but the mechanism decoding these cues is unclear. Here, the authors show that combinatorial TALE/HOX activity destabilizes nucleosomes at WNT-responsive regions to activate paraxial mesodermal genes.

    • Luca Mariani
    • , Xiaogang Guo
    •  & Elisabetta Ferretti
  • Article
    | Open Access

    Skeletal muscle stem cells (or satellite cells, SCs) are normally quiescent but activate and expand in response to injury. Here the authors show that induction of DHX36 helicase during SC activation promotes mRNA translation by binding to 5′UTR mRNA G-quadruplexes (rG4) in targets including Gnai2 and unwinding them.

    • Xiaona Chen
    • , Jie Yuan
    •  & Huating Wang
  • Article
    | Open Access

    Tendon self-renewal occurs rarely and reconstructive surgery comes with significant limitations. Here the authors present an induced pluripotent stem cell-based method to generate tenocytes, analyze their developmental trajectory using scRNA-seq, and demonstrate their contribution to motor function recovery after Achilles tendon injury via engraftment and paracrine effects.

    • Taiki Nakajima
    • , Akihiro Nakahata
    •  & Makoto Ikeya
  • Article
    | Open Access

    T cells derived from stem cells can be harnessed for regenerative medicine and cancer immunotherapy, but current technologies limit production and translation. Here, the authors present a serum-free, stromal-cell free DLL4-coated microbead method for the scalable production of T-lineage cells from multiple sources of stem cells.

    • Ashton C. Trotman-Grant
    • , Mahmood Mohtashami
    •  & Juan Carlos Zúñiga-Pflücker
  • Article
    | Open Access

    The authors form pre-epicardial cells (PECs) from hiPSC-derived lateral plate mesoderm on treating with BMP4, RA and VEGF, and co-culture these PECs with cardiomyocytes, inducing cardiomyocyte aggregation, proliferation and network formation with more mature structures and improved beating/contractility.

    • Jun Jie Tan
    • , Jacques P. Guyette
    •  & Harald C. Ott
  • Article
    | Open Access

    Embryos at the 2-cell (2C) stage are totipotent, and overexpression of Dux transcription factor convert embryonic stem cells (ESCs) to a 2C-like state. Here the authors show that DUX-mediated 2C-like reprogramming is associated with DNA damage at CTCF sites and CTCF depletion promotes 2Clike conversion.

    • Teresa Olbrich
    • , Maria Vega-Sendino
    •  & Sergio Ruiz
  • Article
    | Open Access

    RPAP3 is a subunit of the R2TP complex, a co-chaperone of HSP90, with substrate proteins involved in transcription, ribosome biogenesis, DNA repair and cell growth. Here the authors report that deletion of Rpap3 abrogates cell proliferation and homeostasis in mouse intestine, partly through destabilization of PI3K-like kinases, while elevated RPAP3 levels in colorectal tumors are associated with poor prognosis.

    • Chloé Maurizy
    • , Claire Abeza
    •  & Bérengère Pradet-Balade
  • Article
    | Open Access

    Organoids have improved disease modeling. Here, the authors generate human sensorimotor organoids derived from hiPSCs of individuals with ALS. These organoids contain skeletal muscle, sensory and motor neurons as well as astrocytes, microglia, and vasculature and form neuromuscular junctions.

    • João D. Pereira
    • , Daniel M. DuBreuil
    •  & Brian J. Wainger
  • Article
    | Open Access

    Cranial sutures are major growth centers for the skull vault and premature fusion leads to pathological fusion, craniosynostosis. Here the authors isolate Wnt responsive skeletal stem and progenitor cells from sutures, that can be transplanted together with Wnt3a protein to repair craniosynostosis in a mouse model.

    • Siddharth Menon
    • , Ankit Salhotra
    •  & Natalina Quarto
  • Article
    | Open Access

    Differentiation of hPSCs to cardiomyocytes suffers from high variability. Here the authors report a label-free live cell imaging platform based on autofluorescence imaging to enable the prediction of cardiomyocyte differentiation efficiency from hPSCs.

    • Tongcheng Qian
    • , Tiffany M. Heaster
    •  & Melissa C. Skala
  • Article
    | Open Access

    Retinoblastoma is a heritable pediatric cancer driven by mutations in RB1. Here, the authors demonstrate the first patient derived model of retinoblastoma using iPSCs from patients with germline mutations in RB1.

    • Jackie L. Norrie
    • , Anjana Nityanandam
    •  & Michael A. Dyer
  • Article
    | Open Access

    BRAF-MAPK activating mutations are reported in histiocytoses—hematological neoplasms with widespread pro-inflammatory myeloid cells. Here, the authors show that an activating mutant BRAF in haematopoietic stem and progenitor cells causes an oncogene-induced senescence response leading to myeloid restricted haematopoiesis, inflammation and histiocytosis.

    • Riccardo Biavasco
    • , Emanuele Lettera
    •  & Eugenio Montini
  • Article
    | Open Access

    Quantitative methods to assess the quality of hPSC-derived organoids have not been developed. Here they present a prediction algorithm to assess the transcriptomic similarity between hPSC-derived organoids and the corresponding human target organs and perform validation on lung bud organoids, antral gastric organoids, and cardiomyocytes.

    • Mi-Ok Lee
    • , Su-gi Lee
    •  & Hyun-Soo Cho
  • Article
    | Open Access

    Reactive oxygen species (ROS) are metabolic by-products which in excess can be toxic for hematopoietic stem and progenitor cells (HSPCs). Here the authors show that toxic ROS are transferred by expanding HSPCs to the zebrafish developmental niche via connexin Cx41.8, where Ifi30 promotes their detoxification.

    • Pietro Cacialli
    • , Christopher B. Mahony
    •  & Julien Y. Bertrand
  • Article
    | Open Access

    Vasculogenic mimicry (VM) contributes to the development of triple-negative breast cancer. In this study, the authors show that TEM8 is expressed in VM-forming breast cancer stem cells and it promotes stemness and VM differentiation capacity through a RhoC/ROCK1/SMAD5 axis

    • Jiahui Xu
    • , Xiaoli Yang
    •  & Suling Liu
  • Article
    | Open Access

    Different types of mesenchymal progenitors participate in ectopic bone formation. Here, the authors show Col2+ lineage cells adopt a lymphatic endothelium cell fate, which regulates local inflammatory microenvironment after trauma, thus influencing heterotopic ossification (HO) development via a FGFR3-BMPR1a pathway.

    • Dali Zhang
    • , Junlan Huang
    •  & Yangli Xie
  • Article
    | Open Access

    The transcriptional regulators underlying the induction and differentiation of dense connective tissues remain largely unknown. Here the authors generate tendon and fibrocartilage cells from mouse embryonic stem cells and apply scRNA-seq to identify molecular regulation of the cell fate switch between these lineages.

    • Deepak A. Kaji
    • , Angela M. Montero
    •  & Alice H. Huang
  • Article
    | Open Access

    Few studies have provided functional analysis of the epigenetic landscape in the regenerating liver. Here the authors define chromatin states in the quiescent vs. regenerating mouse liver through integration of genome wide profiles of DNA methylation, histone modifications, and chromatin accessibility, identifying H3K27me3 as an epigenetic mark conferring regenerative potential.

    • Chi Zhang
    • , Filippo Macchi
    •  & Kirsten C. Sadler
  • Article
    | Open Access

    Emerging evidence suggests that exit from pluripotency is a regulated, rather than passive process. Here the authors identify a requirement for SS18-mediated Brg/Brahma-associated factors (BAF) chromatin remodeling complex assembly during exit from pluripotency, and that SS18 promotes BAF assembly through liquidliquid phase separation.

    • Junqi Kuang
    • , Ziwei Zhai
    •  & Duanqing Pei
  • Article
    | Open Access

    Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

    • Yu-chi Shen
    • , Adrienne Niederriter Shami
    •  & Saher Sue Hammoud
  • Article
    | Open Access

    Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) suffer from limited maturation. Here the authors identify ERRγ agonist as a factor that enhances cardiac morphological, metabolic, contractile and electrical maturation of hiPSC-derived CMs with T-tubule formation.

    • Kenji Miki
    • , Kohei Deguchi
    •  & Yoshinori Yoshida
  • Article
    | Open Access

    The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m6A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m6A methylation activity of the complex.

    • Xiaona Liu
    • , Hailong Wang
    •  & Shan Xiao
  • Article
    | Open Access

    Bone marrow chimaeric mice are a valuable tool in research, but require myeloablative conditioning. Here the authors demonstrate efficient FACS-free enrichment of haematopoietic stem and progenitor cells for transplantation into unconditioned recipient mice, as well as for genetic engineering using polyvinyl alcohol based media.

    • Kiyosumi Ochi
    • , Maiko Morita
    •  & Satoshi Yamazaki
  • Article
    | Open Access

    Both A/B compartments and TADs are thought to be absent from the inactive X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, the authors characterise gene reactivation, chromatin opening and chromosome topology during X-reactivation, observe A/B-like compartments on the inactive X that guide TAD formation independently of transcription during X-reactivation.

    • Moritz Bauer
    • , Enrique Vidal
    •  & Bernhard Payer
  • Article
    | Open Access

    The epigenetic mechanisms coordinating the maintenance of adult cellular lineages remain poorly understood. Here the authors demonstrate that HIRA, a H3.3 histone chaperone, establishes the chromatin landscape required for skeletal muscle cell identity.

    • Joana Esteves de Lima
    • , Reem Bou Akar
    •  & Frédéric Relaix