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Article
| Open AccessAn epigenetic barrier sets the timing of human neuronal maturation
The slow maturation of human neurons is regulated by epigenetic modification in nascent neurons, mediated by EZH2, EHMT1, EHMT2 and DOT1L.
- Gabriele Ciceri
- , Arianna Baggiolini
- & Lorenz Studer
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Article
| Open AccessTransgenic ferret models define pulmonary ionocyte diversity and function
Conditional genetic ferret models enable ionocyte lineage tracing, ionocyte ablation and ionocyte-specific deletion of CFTR to elucidate the roles of pulmonary ionocyte biology and function during human health and disease.
- Feng Yuan
- , Grace N. Gasser
- & John F. Engelhardt
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Article
| Open AccessPluripotent stem cell-derived model of the post-implantation human embryo
Co-culture of wild-type human embryonic stem cells with two types of extraembryonic-like cell engineered to overexpress specific transcription factors results in an embryoid model that recapitulates multiple features of the post-implantation human embryo.
- Bailey A. T. Weatherbee
- , Carlos W. Gantner
- & Magdalena Zernicka-Goetz
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Article |
Generation of functional oocytes from male mice in vitro
Mouse induced pluripotent stem cells derived from differentiated fibroblasts could be converted from male (XY) to female (XX), resulting in cells that could form oocytes and give rise to offspring after fertilization.
- Kenta Murakami
- , Nobuhiko Hamazaki
- & Katsuhiko Hayashi
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Article |
Reconstruction and deconstruction of human somitogenesis in vitro
Somitoids and segmentoids—culture systems that recapitulate the formation of somite-like structures—reveal that an initial salt-and-pepper expression pattern of MESP2 in a newly formed segment is transformed into compartments of anterior and posterior identity through an active cell-sorting mechanism.
- Yuchuan Miao
- , Yannis Djeffal
- & Olivier Pourquié
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Article |
Reconstituting human somitogenesis in vitro
A 3D model of human segmentation and somitogenesis derived from induced pluripotent stem cells captures the oscillatory dynamics of the segmentation clock as well as morphological and molecular features of the developing embryonic axis and tail.
- Yoshihiro Yamanaka
- , Sofiane Hamidi
- & Cantas Alev
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Article
| Open AccessInferring and perturbing cell fate regulomes in human brain organoids
A multi-omic atlas of brain organoid development facilitates the inference of an underlying gene regulatory network using the newly developed Pando framework and shows—in conjunction with perturbation experiments—that GLI3 controls forebrain fate establishment through interaction with HES4/5 regulomes.
- Jonas Simon Fleck
- , Sophie Martina Johanna Jansen
- & Barbara Treutlein
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Article
| Open AccessEmbryo model completes gastrulation to neurulation and organogenesis
Synthetic mouse embryos assembled from embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells closely recapitulate the development of wild-type and mutant natural mouse embryos up to embryonic day 8.5.
- Gianluca Amadei
- , Charlotte E. Handford
- & Magdalena Zernicka-Goetz
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Article |
Generation of 3D lacrimal gland organoids from human pluripotent stem cells
Organoids originating from human multipotent ocular surface epithelial stem cells are similar to native lacrimal glands and undergo functional maturation when transplanted adjacent to the eyes of recipient rats, developing lumina and producing tear-film proteins.
- Ryuhei Hayashi
- , Toru Okubo
- & Kohji Nishida
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Article |
Obesity accelerates hair thinning by stem cell-centric converging mechanisms
Obesity in mice, caused by a high-fat diet, induces hair loss as a result of changes in the differentiation of hair follicle stem cells.
- Hironobu Morinaga
- , Yasuaki Mohri
- & Emi K. Nishimura
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Article |
Primate cell fusion disentangles gene regulatory divergence in neurodevelopment
Cortical organoids derived from tetraploid human–chimpanzee fused induced pluripotent stem cells provide a platform for untangling unique molecular features of human brain development.
- Rachel M. Agoglia
- , Danqiong Sun
- & Hunter B. Fraser
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Article |
In situ mapping identifies distinct vascular niches for myelopoiesis
A combination of fluorescent antibodies is used to build visual maps of all myeloid cells in the bone marrow, providing new insight into how the bone marrow microenvironment regulates cell-fate decisions.
- Jizhou Zhang
- , Qingqing Wu
- & Daniel Lucas
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Article |
Immune-evasive human islet-like organoids ameliorate diabetes
Metabolically-mature human islet-like organoids generated from induced pluripotent stem cells are able to recapitulate insulin-responsive pancreatic islet function and avoid immunologic cell death in diabetic mouse transplantation models.
- Eiji Yoshihara
- , Carolyn O’Connor
- & Ronald M. Evans
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Article |
Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis
Using single-cell lineage tracing, the authors identify TCF15 as a novel regulator of haematopoietic stem cell quiescence and self-renewal.
- Alejo E. Rodriguez-Fraticelli
- , Caleb Weinreb
- & Fernando D. Camargo
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Article |
Single-molecule imaging of transcription dynamics in somatic stem cells
Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.
- Justin C. Wheat
- , Yehonatan Sella
- & Ulrich Steidl
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Article |
Cell stress in cortical organoids impairs molecular subtype specification
Single-cell RNA sequencing clarifies the development and specification of neurons in the human cortex and shows that cell stress impairs this process in cortical organoids.
- Aparna Bhaduri
- , Madeline G. Andrews
- & Arnold R. Kriegstein
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Article |
In vitro characterization of the human segmentation clock
Human presomitic mesoderm cells derived in vitro demonstrate oscillations of the segmentation clock, thus providing a window into an otherwise inaccessible stage of human development.
- Margarete Diaz-Cuadros
- , Daniel E. Wagner
- & Olivier Pourquié
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Letter |
Organoid single-cell genomic atlas uncovers human-specific features of brain development
Species comparisons using single-cell transcriptomics and accessible chromatin profiling in stem cell-derived cerebral organoids are used to map dynamic gene-regulatory changes that are unique to humans.
- Sabina Kanton
- , Michael James Boyle
- & J. Gray Camp
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Letter |
Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary
Juxtaposition of region-specific gut spheroids derived from human pluripotent stem cells in the absence of extrinsic factors results in development of segregated hepato-biliary-pancreatic anlages that recapitulate early morphogenetic events.
- Hiroyuki Koike
- , Kentaro Iwasawa
- & Takanori Takebe
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Article |
A human liver cell atlas reveals heterogeneity and epithelial progenitors
Single-cell RNA sequencing of cells from healthy human liver, hepatocellular carcinoma and chimaeric mouse liver identifies subtypes of liver cells, epithelial progenitors and differences between healthy and diseased cells.
- Nadim Aizarani
- , Antonio Saviano
- & Dominic Grün
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Letter |
Individual brain organoids reproducibly form cell diversity of the human cerebral cortex
Single-cell RNA-sequencing analysis demonstrates that individual human brain organoids generate the cellular diversity of the cerebral cortex with organoid-to-organoid variability that is comparable to that of individual endogenous brains.
- Silvia Velasco
- , Amanda J. Kedaigle
- & Paola Arlotta
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Article |
Charting cellular identity during human in vitro β-cell differentiation
Single-cell transcriptional profiling of in vitro human pancreatic β-cell differentiation reveals progenitor and terminal fates, produces a detailed time course of endocrine induction and underpins a lineage model.
- Adrian Veres
- , Aubrey L. Faust
- & Douglas A. Melton
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Letter |
Human blood vessel organoids as a model of diabetic vasculopathy
Organoids derived from human stem cells recapitulate the structure and functions of human blood vessels, and can be used to model and identify regulators of diabetic vasculopathy.
- Reiner A. Wimmer
- , Alexandra Leopoldi
- & Josef M. Penninger
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Article |
A revised airway epithelial hierarchy includes CFTR-expressing ionocytes
Single-cell RNA sequencing analysis identifies cell types and lineages in airway epithelium, including the pulmonary ionocyte, a new cell type predominantly expressing the cystic fibrosis gene CFTR.
- Daniel T. Montoro
- , Adam L. Haber
- & Jayaraj Rajagopal
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Letter |
Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination
Many small molecules that stimulate oligodendrocyte formation act not through their canonical pathways but by inhibiting enzymes within the cholesterol biosynthesis pathway and thereby inducing the accumulation of 8,9-unsaturated sterols.
- Zita Hubler
- , Dharmaraja Allimuthu
- & Drew J. Adams
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Letter |
Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells
Binding of an embryonic stem in two cases cell-specific transcription factor pre-marks cell-type-restricted enhancers in embryonic stem in two cases cells, and this premarking is required for the robustness of enhancer activation in differentiated cells.
- Hong Sook Kim
- , Yuliang Tan
- & Michael G. Rosenfeld
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Review Article |
From haematopoietic stem cells to complex differentiation landscapes
- Elisa Laurenti
- & Berthold Göttgens
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Letter |
Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells
Analysis of transplantation of single haematopoietic stem cells in mice defines stable lineage-restricted fates in long-term self-renewing multipotent stem cells, including a class of multipotent stem cells that exclusively replenishes the megakaryocyte/platelet lineage.
- Joana Carrelha
- , Yiran Meng
- & Sten Eirik W. Jacobsen
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Letter |
Clonal analysis of lineage fate in native haematopoiesis
Transposon tagging to clonally trace progenitors and stem cells provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.
- Alejo E. Rodriguez-Fraticelli
- , Samuel L. Wolock
- & Fernando D. Camargo
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Letter |
Pluripotent state transitions coordinate morphogenesis in mouse and human embryos
Exit of epiblasts from an unrestricted naive pluripotent state is required for epithelialization and generation of the pro-amniotic cavity in mouse embryos and for amniotic cavity formation in human embryos and human embryonic stem cells.
- Marta N. Shahbazi
- , Antonio Scialdone
- & Magdalena Zernicka-Goetz
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Letter |
Multilineage communication regulates human liver bud development from pluripotency
Single-cell RNA sequencing analysis of two- and three-dimensional hepatic differentiation reveals that both systems recapitulate certain transcriptomic features of human hepatogenesis.
- J. Gray Camp
- , Keisuke Sekine
- & Barbara Treutlein
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Article |
Haematopoietic stem and progenitor cells from human pluripotent stem cells
Haematopoietic stem and progenitor cell conversion of human pluripotent stem cell-derived haemogenic endothelium.
- Ryohichi Sugimura
- , Deepak Kumar Jha
- & George Q. Daley
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Letter |
Interplay between metabolic identities in the intestinal crypt supports stem cell function
The glycolytic activity of Paneth cells provides lactate, which is required by self-renewing intestinal stem cells for oxidative metabolism to activate p38 MAP kinase, ensuring regeneration of a mature crypt.
- Maria J. Rodríguez-Colman
- , Matthias Schewe
- & Boudewijn M. T. Burgering
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Article |
Wnt/β-catenin promotes gastric fundus specification in mice and humans
Wnt signalling is shown to be required for specification of the gastric fundus in mice, and was used to develop human gastric organoids with functional fundic cell types.
- Kyle W. McCracken
- , Eitaro Aihara
- & James M. Wells
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Letter |
Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease
A differentiation protocol to obtain enteric nervous system (ENS) progenitors and a range of neurons from human pluripotent stem cells is developed; the cells can migrate and graft to the colon of a chick embryo and an adult mouse colon, including in a mouse model of Hirschsprung disease, in which a functional rescue is observed.
- Faranak Fattahi
- , Julius A Steinbeck
- & Lorenz Studer
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Letter |
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
The kidney arises from two types of progenitors; here, the signalling conditions that induce the production of collecting ducts and functional nephrons from human pluripotent stem cells are determined, and organoids that recapitulate the functional regionalization of the kidney are produced.
- Minoru Takasato
- , Pei X. Er
- & Melissa H. Little
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Letter |
Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice
An analysis of mouse skin reveals that super-enhancers are critical to identity, lineage commitment and plasticity of adult stem cells; dynamic super-enhancer remodelling in new niches is dependent on the levels of pioneer transcription factor SOX9, which is identified as a key regulator of super-enhancer chromatin for hair follicle stem cells.
- Rene C. Adam
- , Hanseul Yang
- & Elaine Fuchs
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Article
| Open AccessTranscription factor binding dynamics during human ES cell differentiation
Lineage-specific transcription factors and signalling pathways cooperate with pluripotency regulators to control the transcriptional networks that drive cell specification and exit from an embryonic stem cell state; here, we report genome-wide binding data for 38 transcription factors combined with analysis of epigenomic and gene expression data during the differentiation of human embryonic stem cells into the three germ layers.
- Alexander M. Tsankov
- , Hongcang Gu
- & Alexander Meissner
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Article |
In situ identification of bipotent stem cells in the mammary gland
Through the use of a novel three-dimensional imaging technique, used in conjunction with a multicolour reporter that allows lineage tracing and cell tracking of entire mammary ducts in vivo, bipotent stem cells are shown to have a central role in both puberty and long-term maintenance; in addition, long-lived luminal progenitor cells with a prominent role in ductal expansion are identified.
- Anne C. Rios
- , Nai Yang Fu
- & Jane E. Visvader
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Article |
Generation of functional thyroid from embryonic stem cells
Transient overexpression of the transcription factors NKX2-1 and PAX8 in a murine cell model is shown to direct the differentiation of embryonic stem cells towards a thyroid follicular cell lineage; the resulting three-dimensional thyroid follicles created by subsequent thyrotropin treatment show hallmarks of thyroid function in vitro and rescue thyroid function in vivo when transplanted into athyroid mice, adding to our understanding of the molecular mechanisms underlying thyroid development.
- Francesco Antonica
- , Dominika Figini Kasprzyk
- & Sabine Costagliola
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News & Views |
A sporadic super state
It seems that embryonic stem cells regularly pass through a transient state during which they can generate all the cell types of an animal, including those of the placenta. See Article p.57
- Azim Surani
- & Julia Tischler
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Letter |
Enhancer decommissioning by LSD1 during embryonic stem cell differentiation
In embryonic stem cells, the histone demethylase LSD1 occupies the enhancers of active genes and, together with the NuRD complex, decommissions the enhancers during differentiation.
- Warren A. Whyte
- , Steve Bilodeau
- & Richard A. Young
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Letter |
JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells
Polycomb proteins have a key role in regulating the expression of genes essential for development, differentiation and maintenance of cell fates. Here, Polycomb repressive complex 2 (PRC2) is shown to form a complex with JARID2, a Jumonji domain protein. JARID2 is required for the binding of Polycomb proteins to target genes in embryonic stem cells as well as for the proper differentiation of ES cells.
- Diego Pasini
- , Paul A. C. Cloos
- & Kristian Helin