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| Open AccessHypoblast from human pluripotent stem cells regulates epiblast development
Authentic hypoblast cells created from naive human pluripotent stem cells (hPSCs) spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity.
- Takumi Okubo
- , Nicolas Rivron
- & Yasuhiro Takashima
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Article
| Open AccessComplete human day 14 post-implantation embryo models from naive ES cells
The culture of genetically unmodified human naive embryonic stem cells in specific growth conditions gives rise to structures that recapitulate those of post-implantation human embryos up to 13–14 days after fertilization.
- Bernardo Oldak
- , Emilie Wildschutz
- & Jacob H. Hanna
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Article |
Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease
In mouse and rat models of Parkinson’s disease, co-transplanting regulatory T cells (Treg cells) improves the survival of grafted midbrain dopamine neurons in cell therapies by reducing the inflammatory response caused by surgical injury.
- Tae-Yoon Park
- , Jeha Jeon
- & Kwang-Soo Kim
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Article
| Open AccessSelf-patterning of human stem cells into post-implantation lineages
Human pluripotent stem cells can be triggered to self-organize into structures recapitulating early human post-implantation embryonic development.
- Monique Pedroza
- , Seher Ipek Gassaloglu
- & Berna Sozen
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Article
| Open AccessIntegrated intracellular organization and its variations in human iPS cells
A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.
- Matheus P. Viana
- , Jianxu Chen
- & Susanne M. Rafelski
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Article |
Spatial profiling of early primate gastrulation in utero
3D transcriptomes reveal the molecular code of lineage specification in the primate embryo and provide an in vivo reference to decipher human development.
- Sophie Bergmann
- , Christopher A. Penfold
- & Thorsten E. Boroviak
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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 |
Chemical reprogramming of human somatic cells to pluripotent stem cells
Human somatic cells were reprogrammed to human chemically induced pluripotent stem cells that demonstrate key features of embryonic stem cells.
- Jingyang Guan
- , Guan Wang
- & Hongkui Deng
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Article |
Single-cell transcriptomic characterization of a gastrulating human embryo
The single-cell transcriptional profile of a human embryo between 16 and 19 days after fertilization reveals parallels and differences in gastrulation in humans as compared with mouse and non-human primate models.
- Richard C. V. Tyser
- , Elmir Mahammadov
- & Shankar Srinivas
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Article |
Blastocyst-like structures generated from human pluripotent stem cells
An in vitro culture strategy enables the generation of blastocyst-like structures termed human blastoids from naive human pluripotent stem cells, providing a model for studying human embryogenesis.
- Leqian Yu
- , Yulei Wei
- & Jun Wu
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Article |
Cell competition constitutes a barrier for interspecies chimerism
Primed pluripotent stem cells from distant species compete with each other, and inactivation of NF-κB signalling in normally outcompeted human cells improves their survival and chimerism in mouse embryos.
- Canbin Zheng
- , Yingying Hu
- & Jun Wu
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Article |
Reconstitution of the oocyte transcriptional network with transcription factors
Eight transcription factors are identified that, when overexpressed, are sufficient to grow oocyte-like cells from mouse pluripotent stem cells.
- Nobuhiko Hamazaki
- , Hirohisa Kyogoku
- & Katsuhiko Hayashi
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Article |
Reprogramming roadmap reveals route to human induced trophoblast stem cells
Single-cell transcriptomics roadmap of human dermal fibroblasts reprogrammed to primed and naive pluripotency reveals a route for the direct reprogramming of somatic cells into induced trophoblast stem cells.
- Xiaodong Liu
- , John F. Ouyang
- & Jose M. Polo
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Article |
Intracellular pH controls WNT downstream of glycolysis in amniote embryos
The authors show that metabolic activity leads to an increase in the intracellular pH of neuromesodermal precursors, and that this increase in pH, by allowing post-translational modification of β-catenin, is required for the activation of WNT signalling and mesodermal fate acquisition.
- Masayuki Oginuma
- , Yukiko Harima
- & Olivier Pourquié
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Article |
Recapitulating the human segmentation clock with pluripotent stem cells
A system involving in vitro induction of presomitic mesoderm recapitulates oscillatory expression of core segmentation clock genes and travelling-wave-like gene expression, suggesting that this system can be used to study the human segmentation clock and provide insights into diseases associated with human axial skeletogenesis.
- Mitsuhiro Matsuda
- , Yoshihiro Yamanaka
- & Cantas Alev
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Article |
Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing
Fibroblasts from old mice are heterogeneous, which affects the ability of these fibroblasts to reprogram into induced pluripotent stem cells in vitro and influences wound healing rate in vivo.
- Salah Mahmoudi
- , Elena Mancini
- & Anne Brunet
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Letter |
Molecular architecture of lineage allocation and tissue organization in early mouse embryo
Spatially resolved transcriptomes of cell populations at defined positions in the early mouse embryo reveal molecular bases of lineage specification and tissue patterning.
- Guangdun Peng
- , Shengbao Suo
- & Naihe Jing
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Letter |
Linking a cell-division gene and a suicide gene to define and improve cell therapy safety
Introduction of a suicide gene together with a linked cell-division gene to generate a safe-cell system enables the selective elimination of proliferating cells after cell transplantation in mouse models of cell therapy.
- Qin Liang
- , Claudio Monetti
- & Andras Nagy
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Letter |
OTX2 restricts entry to the mouse germline
The transcription factor OTX2 ensures that germline induction is initially kept in check and only proceeds after OTX2 downregulation.
- Jingchao Zhang
- , Man Zhang
- & Ian Chambers
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Letter |
An orthogonal proteomic survey uncovers novel Zika virus host factors
Integrative analyses identify host proteins that are modulated by Zika virus at multiple levels and provide a comprehensive framework for the understanding of Zika virus-induced changes to cellular pathways.
- Pietro Scaturro
- , Alexey Stukalov
- & Andreas Pichlmair
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Letter |
Blastocyst-like structures generated solely from stem cells
Trophoblast and embryonic stem cells interact in vitro to form structures that resemble early blastocysts, and the embryo provides signals that drive early trophectoderm development and implantation.
- Nicolas C. Rivron
- , Javier Frias-Aldeguer
- & Niels Geijsen
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Letter |
Advanced maturation of human cardiac tissue grown from pluripotent stem cells
A tissue culture system that provides an increasing intensity of electromechanical stimulation over time enables an in vitro model of cardiac tissue derived from human induced pluripotent stem cells to develop many of the characteristics of adult cardiac tissue.
- Kacey Ronaldson-Bouchard
- , Stephen P. Ma
- & Gordana Vunjak-Novakovic
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Article |
Genome editing reveals a role for OCT4 in human embryogenesis
Genome editing in human zygotes shows that OCT4 is required for normal development at an earlier stage in humans than in mice.
- Norah M. E. Fogarty
- , Afshan McCarthy
- & Kathy K. Niakan
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Letter |
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model
In a preclinical study, dopaminergic neurons derived from human induced pluripotent stem cells were implanted into a primate model of Parkinson’s disease, where they were found to exhibit long-term survival, function as mid-brain dopaminergic neurons, and increase spontaneous movements.
- Tetsuhiro Kikuchi
- , Asuka Morizane
- & Jun Takahashi
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Article |
Common genetic variation drives molecular heterogeneity in human iPSCs
Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease.
- Helena Kilpinen
- , Angela Goncalves
- & Daniel J. Gaffney
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Article |
Cell diversity and network dynamics in photosensitive human brain organoids
Long-term cultures of human brain organoids display a high degree of cellular diversity, mature spontaneous neuronal networks and are sensitive to light.
- Giorgia Quadrato
- , Tuan Nguyen
- & Paola Arlotta
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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 |
Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts
Allogenic induced pluripotent stem cell-derived cardiomyocytes transplanted directly into infarcted cynomolgus monkey hearts show electrical coupling with host cardiomyocytes improve cardiac contractile function after mild immunosuppression.
- Yuji Shiba
- , Toshihito Gomibuchi
- & Uichi Ikeda
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Article |
A developmental coordinate of pluripotency among mice, monkeys and humans
Using a single-cell sequencing analysis in monkey embryos, and comparing the genes expressed during early development in this species with those in mice and in human pluripotent stem cells, the authors define characteristics of pluripotency ontogeny across mammalian species.
- Tomonori Nakamura
- , Ikuhiro Okamoto
- & Mitinori Saitou
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Letter |
Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9
A CRISPR/Cas9 genome editing framework has been developed that allows controlled introduction of mono- and bi-allelic sequence changes, and is used to generate induced human pluripotent stem cells with heterozygous and homozygous dominant mutations in amyloid precursor protein and presenilin 1 that have been associated with early onset Alzheimer’s disease.
- Dominik Paquet
- , Dylan Kwart
- & Marc Tessier-Lavigne
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Letter |
Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression
A CRISPR/Cas9 system is used to dissect the role of allelic risk variants on the expression of the α-synuclein gene SNCA, which has been linked to Parkinson’s disease development.
- Frank Soldner
- , Yonatan Stelzer
- & Rudolf Jaenisch
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Letter |
Derivation and differentiation of haploid human embryonic stem cells
Haploid human embryonic stem cells have been derived from haploid oocytes, the cells maintain a normal haploid karyotype as pluripotent cells and, unexpectedly, as differentiated cells — loss-of-function genetic screens previously performed with haploid embryonic stem cells in mice can now be performed in humans.
- Ido Sagi
- , Gloryn Chia
- & Nissim Benvenisty
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Letter |
Co-ordinated ocular development from human iPS cells and recovery of corneal function
A protocol has been developed to use human induced pluripotent stem cells to obtain a self-formed ectodermal autonomous multizone, which includes distinct cell lineages of the eye, including the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium that can be expanded to form a functional corneal epithelium when transplanted to an animal model of corneal visual impairment.
- Ryuhei Hayashi
- , Yuki Ishikawa
- & Kohji Nishida
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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 |
NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers
In mouse embryonic stem cells converted to an epiblast fate in vitro—a state in which the cells can also gain germ cell fate if exposed to the signalling molecule BMP4—the sole expression of the transcription factor NANOG is shown to be sufficient to induce germ cell fate, in the absence of BMP4.
- Kazuhiro Murakami
- , Ufuk Günesdogan
- & M. Azim Surani
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Article |
The histone chaperone CAF-1 safeguards somatic cell identity
RNA interference screens were used to identify chromatin-associated factors that impede reprogramming of somatic cells into iPS cells; suppression of the chromatin assembly factor CAF-1 enhances the generation of iPS cells by rendering chromatin more accessible to pluripotency transcription factors.
- Sihem Cheloufi
- , Ulrich Elling
- & Konrad Hochedlinger
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Letter |
Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder
A neuronal model of bipolar disorder based on induced pluripotent stem cell (iPSC) technology finds hyperactive action-potential firing and differential responsiveness to lithium in iPSC-derived neurons from patients with bipolar disorder.
- Jerome Mertens
- , Qiu-Wen Wang
- & Jun Yao
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Brief Communications Arising |
Failure to replicate the STAP cell phenomenon
- Alejandro De Los Angeles
- , Francesco Ferrari
- & George Q. Daley
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Brief Communications Arising |
STAP cells are derived from ES cells
- Daijiro Konno
- , Takeya Kasukawa
- & Fumio Matsuzaki
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Review Article |
Hallmarks of pluripotency
In response to the need for a defined set of criteria to assess stem-cell potency, this review proposes guidelines for the evaluation of newly derived pluripotent stem cells, from functional assays to integrative molecular analyses of transcriptional, epigenetic and metabolic states.
- Alejandro De Los Angeles
- , Francesco Ferrari
- & George Q. Daley
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Article |
An alternative pluripotent state confers interspecies chimaeric competency
A previously unknown type of stem cell that can engraft in specific regions of the mouse epiblast is described; these region-selective pluripotent stem cells display notable intra- and inter-specific chimaera competency and will help to further our understanding of mammalian development.
- Jun Wu
- , Daiji Okamura
- & Juan Carlos Izpisua Belmonte
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Letter |
Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo
Two drugs, miconazole and clobetasol, have functions that modulate differentiation of oligodendrocyte progenitor cells directly, enhance remyelination, and significantly reduce disease severity in mouse models of multiple sclerosis.
- Fadi J. Najm
- , Mayur Madhavan
- & Paul J. Tesar
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Letter |
Early reprogramming regulators identified by prospective isolation and mass cytometry
Identification of transient early induced pluripotency reprogramming intermediates allows for mechanistic insight into the reprogramming process.
- Ernesto Lujan
- , Eli R. Zunder
- & Marius Wernig
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Article |
Genome-wide characterization of the routes to pluripotency
This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.
- Samer M. I. Hussein
- , Mira C. Puri
- & Andras Nagy
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Letter |
Modelling human development and disease in pluripotent stem-cell-derived gastric organoids
The in vitro generation, from pluripotent stem cells, of three-dimensional human gastric organoids (hGOs) that contain a physiological gastric epithelium comprising both progenitor and differentiated cell types, and have expected functional characteristics is described, as is modelling the pathophysiological response of the human stomach to Helicobacter pylori using these hGOs.
- Kyle W. McCracken
- , Emily M. Catá
- & James M. Wells
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Article |
Statin treatment rescues FGFR3 skeletal dysplasia phenotypes
This study reprograms fibroblasts from thanatophoric dysplasia type I (TD1) and achondroplasia (ACH) patients into induced pluripotent stem cells (iPSCs), finding that chondrogenic differentiation results in the formation of degraded cartilage; statin treatment led to significant recovery of bone growth in a mouse model of ACH.
- Akihiro Yamashita
- , Miho Morioka
- & Noriyuki Tsumaki
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Letter |
Mechanism of Dis3l2 substrate recognition in the Lin28–let-7 pathway
The structure of mouse Dis3l2 bound to an oligoU substrate shows a funnel-like substrate-binding site with the RNA being fed into the active site along a path that is distinct from that seen in the related catalytic subunit of the exosome — 12 uracils of the oligoU-tailed RNA are recognized in a complex network of interactions, suggesting the basis for target specificity.
- Christopher R. Faehnle
- , Jack Walleshauser
- & Leemor Joshua-Tor
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Letter |
C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells
A pulse of C/EBPα followed by overexpression of the transcription factors Oct4, Sox2, Klf4 and Myc leads to fast and very efficient reprogramming of B cell precursors to induced pluripotent stem cells; C/EBPα facilitates transient chromatin accessibility and accelerates expression of pluripotency genes through a mechanism that involves activation of the Tet2 enzyme.
- Bruno Di Stefano
- , Jose Luis Sardina
- & Thomas Graf