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3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages

ABSTRACT: 3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages

PROVIDER: PRJNA941800 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23722848_1.fastq.gz	Fastqsanger.gz
	SRR23722848_2.fastq.gz	Fastqsanger.gz
	SRR23722849_1.fastq.gz	Fastqsanger.gz
	SRR23722849_2.fastq.gz	Fastqsanger.gz
	SRR25496984_1.fastq.gz	Fastqsanger.gz

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3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages

Project description:Naïve human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures (“blastoids”) that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick 3D extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day 21. We also show that modulation of WNT signaling alters the balance between epiblast and trophoblast fates in post-implantation blastoids. This work demonstrates that 3D-cultured blastoids offer a continuous and integrated in vitro model system of human embryonic and extraembryonic development from pre-implantation to early gastrulation stages.

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Project description:Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Appropriate stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGF-β, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation analogs of the three founding lineages (trophoblast, epiblast, primitive endoderm; >97%) according to the sequence and pace of blastocyst development. Blastoids spontaneously form an axis marked by the maturation of the polar region, which acquires the potential to specifically attach to hormonally stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development.

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