Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification

Cell stem cell, Год журнала: 2024, Номер 31(7), С. 1058 - 1071.e5

Опубликована: Май 31, 2024

The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in blastocyst. Research with human embryos challenging. Thus, stem models that reproduce differentiation provide valuable alternatives. We show here naive pluripotent (PSC) to proceeds via reversion a transitional ICM-like state from which emerges concordance trajectory blastocysts. identified window when fibroblast growth factor (FGF) signaling critical for specification. Revisiting FGF revealed inhibition early blastocyst suppresses formation. In vitro, induction of synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports establishes conservation lineage specification between mice humans. Overall, this study demonstrates utility PSC-based elucidating mechanistic features embryogenesis.

Язык: Английский

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Propagating pluripotency – The conundrum of self‐renewal

BioEssays, Год журнала: 2024, Номер 46(12)

Опубликована: Авг. 23, 2024

Abstract The discovery of mouse embryonic stem cells in 1981 transformed research mammalian developmental biology and functional genomics. subsequent generation human pluripotent (PSCs) the development molecular reprogramming have opened unheralded avenues for drug cell replacement therapy. Here, I review history PSCs from perspective that long‐term self‐renewal is a product vitro signaling environment, rather than an intrinsic feature embryos. discuss relationship between states captured to stages epiblast embryo suggest key considerations evaluation PSCs. A remaining fundamental challenge determine whether naïve pluripotency can be propagated broad range mammals by exploiting common principles gene regulatory architecture.

Язык: Английский

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Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ self-renewal requirements extraembryonic lineage potency. Here, we investigated generation chimpanzee PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that is enabled inhibition Polycomb repressive complex 2 (PRC2). Expanded show global transcriptome proximity embryo pre-implantation epiblast, with shared expression a subset pluripotency transcription factors. Chimpanzee can transition multilineage competence differentiate into trophectoderm hypoblast, forming tri-lineage blastoids. They thus provide higher primate comparative model for studying embryogenesis. Genetic deletions confirm PRC2 mediates growth arrest. Further, overcomes roadblock feeder-free propagation Therefore, excess deposition chromatin modification H3K27me3 an unexpected barrier PSC self-renewal.

Язык: Английский

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Milestones of Trophectoderm and Naïve-to-Primed Pluripotency Transition in Human Embryos Reveals Stage-Match of Human Blastoids

Опубликована: Янв. 1, 2025

Язык: Английский

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