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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells with properties of the early post-implantation epiblast

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206713 | GEO | 2022/11/13

REPOSITORIES: GEO

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells with properties of the early post-implantation epiblast.

Project description:In the mammalian embryo, a formative pluripotent phase is proposed to exist at the early post-implantation period, during the transition from the pre-implantation naive-to the post-implantation primed-epiblast. By recapitulating a laminin component of the extracellular matrix niche during embryonic formative transition, and defined culture conditions, we generated cultures highly enriched for self-renewing human pluripotent stem cells (hPSCs), exhibiting properties of early post-implantation epiblast cells. These hPSCs display post-implantation-epiblast gene expression profiles. FGF and TGF-β signaling maintain their self-renewal for multiple passages. They have inactive canonical Wnt signaling, do not express primitive streak markers, and are competent to initiate differentiation toward germline and somatic fates. hPSCs exhibiting early post-implantation epiblast properties may shed light on human embryonic PSCs development and may serve for initiating somatic and germ cell specification.

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [LN_hPSC_SC]

Project description:In our study we sought to develop cultures highly enriched for self-renewing human pluripotent stem cells (hPSCs) with an early post-implantation phenotype, capturing the formative pluripotency phase in vitro. Our results demonstrate that hPSCs cultured on LN111 in defined conditions (LN-hPSCs) generate cultures highly enriched for genetically stable, self-renewing hPSCs exhibiting properties similar to the early-post implantation epiblast, including competence to give rise to the germ cell lineage. To analyze the global transcriptome of LN-hPSCs in comparison with conventional/primed and naive hPSCs, we performed RNA-seq of the three hPSC lines cultured under LN, primed, and naïve conditions.

2022-11-13 | GSE206712 | GEO

Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [LN_hPSC_RRBS]

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [Bulk_RNA_Seq]

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells with properties of the early post-implantation epiblast

Project description:Laminin111-based defined culture promoting self-renewing human pluripotent stem cells with properties of the early post-implantation epiblast

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [LN_hPSC_RRBS]

Project description:Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [LN_hPSC_RRBS]

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Laminin111-based defined culture promoting self-renewing human pluripotent stem cells exhibiting properties of early post-implantation epiblast cells [Bulk_RNA_Seq]

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Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells.

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Project description:Pluripotent epiblast stem cells (EpiSCs) derived from postimplantation embryos exhibit properties that are characteristically different when compared with pluripotent embryonic stem cells (ESCs) derived from mouse blastocysts. However, EpiSCs are relatively less well characterised compared with ESCs. In particular, the relationship between EpiSCs and primordial germ cells (PGCs) is unknown, and is worthy of investigation because PGCs originate from postimplantation epiblast cells in vivo. We show that EpiSCs have an infinite capacity for generating PGCs, under conditions that sustain their pluripotency and self-renewal. These PGCs generated in vitro show appropriate transcriptional and epigenetic reprogramming events and are able to develop further into late germ cells. Notably, the PGCs can, in turn, be induced to undergo dedifferentiation into pluripotent embryonic germ cells (EGCs), which resemble ESCs and not the EpiSC from which they are derived. Our observations demonstrate intrinsic reprogramming during specification of PGCs that results in the erasure of epigenetic memory of EpiSCs following reactivation of the X-chromosome, DNA demethylation and re-expression of key pluripotency genes. This study provides novel insights into the nature and properties of EpiSCs, and introduces an in vitro model system that will be useful for investigations on PGC specification and on mechanisms regulating epigenetic reprogramming in germ cells.

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