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Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates [scRNA-seq]

ABSTRACT: Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates [scRNA-seq]

PROVIDER: PRJNA827587 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18780149_1.fastq.gz	Fastqsanger.gz
	SRR18780149_2.fastq.gz	Fastqsanger.gz

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Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates

Project description:Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates

| PRJNA827586 | ENA

Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates [RNA-seq]

Project description:Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates [RNA-seq]

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Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates [scRNA-seq]

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Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates [RNA-seq]

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Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naive transitioning intermediates.

Project description:Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.

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Modelling human pre-gastulation development by 3D culture of blastoids generated from the primed-to-naive transitioning intermediates

Project description:This SuperSeries is composed of the SubSeries listed below.

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Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously

Project description:Human naïve pluripotent stem cells (hnPSCs) can generate integrated models of blastocysts termed blastoids upon switch to inductive medium. However, the underlying mechanisms remain obscure. Here we report that self-renewing hnPSCs spontaneously and efficiently give rise to blastoids upon three dimensional (3D) suspension culture. The spontaneous blastoids mimic early stage human blastocysts in terms of structure, size, and transcriptome characteristics and are capable of progressing to post-implantation stages. This property is conferred by the glycogen synthase kinase-3 (GSK3) signalling inhibitor IM-12 present in 5iLAF self-renewing medium. IM-12 upregulates oxidative phosphorylation-associated genes that underly the capacity of hnPSCs to generate blastoids spontaneously. Starting from day one of self-organization, hnPSCs at the boundary of all 3D aggregates dedifferentiate into E5 embryo-like intermediates. Intermediates co-express SOX2/OCT4 and GATA6 and by day 3 specify trophoblast fate, which coincides with cavity and blastoid formation. In summary, spontaneous blastoid formation results from 3D culture triggering dedifferentiation of hnPSCs into earlier embryo-like intermediates which are then competent to segregate blastocyst fates.

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