Induced pluripotent stem cells in disease modelling and drug discovery

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(7), P. 377 - 388

Published: Feb. 8, 2019

Language: Английский

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Establishment of porcine and human expanded potential stem cells

Nature Cell Biology, Journal Year: 2019, Volume and Issue: 21(6), P. 687 - 699

Published: June 1, 2019

Language: Английский

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Epigenetic resetting of human pluripotency

Development, Journal Year: 2017, Volume and Issue: 144(15), P. 2748 - 2763

Published: Aug. 1, 2017

Much attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset be expanded feeders with doubling time around 24 h. WNT inhibition stabilises process. transcriptome reset diverges markedly from that primed PSCs shares features inner cell mass (ICM). activate expression primate-specific transposable elements. DNA methylation globally reduced level equivalent in ICM non-random, gain at specific loci. Methylation imprints are mostly lost, however. re-primed undergo tri-lineage differentiation germline specification. In female cells, appearance biallelic X-linked gene transcription indicates reactivation silenced X chromosome. On reconversion status, XIST-induced silencing restores monoallelic expression. facile robust routine accompanying data resources will enable widespread utilisation, interrogation, refinement candidate cells.

Language: Английский

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Human naive epiblast cells possess unrestricted lineage potential

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(6), P. 1040 - 1056.e6

Published: April 7, 2021

Classic embryological experiments have established that the early mouse embryo develops via sequential lineage bifurcations. The first segregated is trophectoderm, essential for blastocyst formation. Mouse naive epiblast and derivative embryonic stem cells are restricted accordingly from producing trophectoderm. Here we show, in contrast, human readily make trophectoderm descendant trophoblast cell types. Trophectoderm was induced rapidly efficiently by inhibition of ERK/mitogen-activated protein kinase (MAPK) Nodal signaling. Transcriptome comparison with substantiated direct formation subsequent differentiation into syncytiotrophoblast, cytotrophoblast, downstream cells. During pluripotency progression potential switches to amnion. Live-cell tracking revealed also able produce Thus, paradigm developmental specification coupled restriction does not apply humans. Instead, plasticity regeneration retained until implantation.

Language: Английский

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Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures

Cell, Journal Year: 2019, Volume and Issue: 179(3), P. 687 - 702.e18

Published: Oct. 1, 2019

Language: Английский

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Deconstructing and reconstructing the mouse and human early embryo

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(8), P. 878 - 887

Published: July 19, 2018

Language: Английский

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Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human preimplantation epiblast

Development, Journal Year: 2018, Volume and Issue: unknown

Published: Jan. 1, 2018

Single-cell profiling techniques create opportunities to delineate cell fate progression in mammalian development. Recent studies have provided transcriptome data from human pre-implantation embryos, total comprising nearly 2000 individual cells. Interpretation of these is confounded by biological factors, such as variable embryo staging and cell-type ambiguity, well technical challenges the collective analysis datasets produced with different sample preparation sequencing protocols. Here, we address issues assemble a complete gene expression time course spanning embryogenesis. We identify key transcriptional features over developmental elucidate lineage-specific regulatory networks. resolve post-hoc assignment blastocyst, define robust prototypes that capture epiblast primitive endoderm lineages. Examination pluripotent stem transcriptomes this framework identifies culture conditions sustain naïve state pertaining inner mass. Our approach thus clarifies understanding both lineage segregation early vitro identity, provides an analytical resource for comparative molecular embryology.

Language: Английский

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Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid

Developmental Cell, Journal Year: 2019, Volume and Issue: 51(6), P. 698 - 712.e8

Published: Dec. 1, 2019

Language: Английский

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Self-organization of stem cells into embryos: A window on early mammalian development

Science, Journal Year: 2019, Volume and Issue: 364(6444), P. 948 - 951

Published: June 6, 2019

Embryonic development is orchestrated by robust and complex regulatory mechanisms acting at different scales of organization. In vivo studies are particularly challenging for mammals after implantation, owing to the small size inaccessibility embryo. The generation stem cell models embryo represents a powerful system with which dissect this complexity. Control geometry, modulation physical environment, priming chemical signals reveal intrinsic capacity embryonic cells make patterns. Adding extraembryonic lineages generates three-dimensional that more autonomous from environment recapitulate many features pre- postimplantation mouse embryo, including gastrulation. Here, we review principles self-organization how they set in motion create an

Language: Английский

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Evaluating totipotency using criteria of increasing stringency

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 49 - 60

Published: Jan. 1, 2021

Language: Английский

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