Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252114 | GEO | 2024/01/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Bulk and single-cell RNA-seq of mouse blastocyst, blastoid Trophoblast stem cells and Embryonic stem cells

Project description:We did bulk and single cell RNA sequencing of blastocysts, blastoids, trophoblast stem cells (TSC) and embryonic stem cells (ESC). The goal of these experiment is to describe the transformations of the transcriptome occurring within cells (TSC, ESC) upon formation of a blastoid. E3.25 and E3.5 blastocysts are used as controls. To this end, we first did RNA sequencing of intact structures (E3.25 and E3.5 blastocysts, blastoids, and parental cell lines). In a different series of experiments, we micro-dissected blastocyst, blastoid or trophosphere structures into single cells, and sequenced their mRNAs, to infer cell identity and transcriptome variations.

2018-05-07 | GSE99786 | GEO

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

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

| PRJNA1061131 | ENA

Human blastoids model blastocyst development and implantation [scRNAseq]

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. Stem cells can form blastocyst models, which we termed blastoid. Here we show that naïve human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGFb, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation (>95%) analogs of the three founding lineages (trophoblast, epiblast, hypoblast), and in the sequential and timely manner of blastocysts. Blastoids spontaneously form an axis marked by 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.

2021-09-15 | GSE177616 | GEO

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.

2023-09-07 | GSE226794 | GEO

Generation of Blastocyst-like Structures from Extended Pluripotent Stem Cells

Project description:A single mouse blastomere from until 8-cell embryo can generate an entire blastocyst. Whether blastomere-like extended pluripotent stem cells (EPS cells) retain a similar generative capacity remains unknown. Here, we established a 3D differentiation system that enabled the generation of blastocyst-like structures from EPS cells (EPS-blastoids) through lineage segregation and self-organization. EPS-blastoids resembled blastocysts in morphology and cell lineage allocation. EPS-blastoids formation recapitulated key morphogenetic events during preimplantation and early postimplantation development in vitro. Upon transfer, some EPS-blastoids underwent implantation, induced decidualization, and generated live, albeit disorganized, tissues in utero. Single cell and bulk RNA-sequencing analysis revealed that EPS-blastoids contained all three blastocyst cell lineages and shared transcriptional similarity with natural blastocysts. We also provide proof-of-concept that EPS-blastoids can be generated from somatic cells via cellular reprograming. EPS-blastoids provide a unique platform for studying early embryogenesis, and pave the way to generate viable synthetic embryos using cultured cells.

2019-08-03 | GSE135289 | GEO

Generation of Blastocyst-like Structures from Extended Pluripotent Stem Cells (single-cell RNA-Seq)

2019-10-17 | GSE135701 | GEO

Single-cell RNA-seq for mouse NrESC-blastoids

Project description:Embryonic stem cells upon extrinsic induction could self-assemble into blastocyst-like structures. However, the intrinsic regulation of such blastoid forming potential remain to be addressed. We discover that the activity of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) in expanded potential stem cell (EPSC) positively correlates with blastoid efficiency and quality. In addition, Nr1h2 agonist, T0901317, improves natural blastocyst development. Surprisingly, Nr1h2-activated ESC (NrESC) is rewired towards a distinct pluripotency state that is capable of self-organizing into blastoids and contribute to embryonic and extraembryonic lineage. We aim at characterizing the NrESC-derived blastoids by single-cell RNA-seq and show that blastoid comprise of epiblast-like, trophectoderm-like and primitive endoderm-like populations, which is the same as blastocyst composition and shows respective gene marker expression for each cluster. Thus, NrESC has attained a unique expanded pluripotency state driven by Nr1h2 activation.

2024-10-23 | GSE217826 | GEO

Highly efficient generation of blastocyst-like structures from mouse totipotent blastomere-like cells

Project description:Mammalian embryogenesis begins with a totipotent zygote. Early embryogenesis can be recapitulated by aggregated extended pluripotent stem cells (EPSCs) in a 3D culture system. However, the efficiency of generating blastoids is low and whether other reported totipotent stem cells retained a similar capacity remains unknown. Here we show that spliceosomal repressed totipotent blastomere-like cells (TBLCs) form blastocyst-like structures when aggregated in 3D microwells with around 80% efficiency. TBLC-blastoids resemble blastocysts in morphology and cell-lineage allocation, show similar transcriptional profile with natural blastocysts and contain more TE cells and fewer undefined intermediate cells compared to blastoids from EPSCs. Moreover, TBLC-blastoids can develop beyond the implantation stage in vitro and induce decidualization after transferred into uterus. In summary, we supply an alternative cell type to generate ameliorated blastoids highly efficiently for studying early mouse embryogenesis.

2022-11-08 | GSE197779 | GEO

Cynomolgus monkey embryo model captures gastrulation and early pregnancy

Project description:Here, we constructed monkey blastoids resembling blastocysts in morphology and transcriptomics using naïve ESCs and optimized protocol. The synthetic blastoids could develop to embryonic disk stage with the structure of yolk sac, chorionic cavity, amnion cavity, primitive streak, connecting stalk along the rostral–caudal axis by in-vitro prolonged culture (IVC). Primordial germ cells, gastrulating cells, visceral endoderm/yolk-sac endoderm, three germ layers and haemato-endothelial progenitors were identified in the monkey blastoid IVC embryo by single-cell transcriptomics or immunostaining. Besides, pregnancies with early gestation sacs were achieved by transferring monkey blastoids to surrogates. Our results revealed the in-vitro gastrulation and in-vivo early pregnancy of primate synthetic embryos, providing a powerful system to dissect primate embryonic development with less ethical concerns and restrict access.

2023-04-06 | GSE218375 | GEO

Human blastoids model blastocyst development and implantation [Bulk RNA-seq]

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.

2021-09-15 | GSE179040 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data