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Human blastoid from primed human embryonic stem cells

ABSTRACT: A human blastoid, which is an artificial human blastocyst, and has a potential as great tool to investigate fundamentals during the development and establish in vitro models to study the pregnancy failure and birth deficiency, without the use of a human embryo. In 2021, although some methods to generate blastoids have been reported, they used human naïve pluripotent stem cells, which often show genomic instability during in vitro culture. Here, we introduce the simple, robust and scalable method to generate human blastoids from more stable human primed embryonic stem cells. By using non-cell-adhesive hydrogel, hESC aggregates received the chemophysical cellular environment, and forming the asymmetric blastoid structure with the cellular distribution like a human blastocyst. The obtained blastoids also showed the capability the implantation in vitro. This model will enable to elucidate the underlying mechanisms of human pre- and post-implantation process, leading to assisted reproductive technology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231484 | GEO | 2024/06/29

REPOSITORIES: GEO

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Human blastoid from primed human embryonic stem cells

Project description:A human blastoid, which is an artificial human blastocyst, and has a potential as great tool to investigate fundamentals during the development and establish in vitro models to study the pregnancy failure and birth deficiency, without the use of a human embryo. In 2021, although some methods to generate blastoids have been reported, they used human naïve pluripotent stem cells, which often show genomic instability during in vitro culture. Here, we introduce the simple, robust and scalable method to generate human blastoids from more stable human primed embryonic stem cells. By using non-cell-adhesive hydrogel, hESC aggregates received the chemophysical cellular environment, and forming the asymmetric blastoid structure with the cellular distribution like a human blastocyst. The obtained blastoids also showed the capability the implantation in vitro. This model will enable to elucidate the underlying mechanisms of human pre- and post-implantation process, leading to assisted reproductive technology.

2024-06-29 | GSE206469 | GEO

Human blastoid from primed human incuded pluripotent stem cells

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

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2021-09-15 | GSE179040 | GEO

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.

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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.

2023-09-07 | GSE226794 | GEO

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: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.

2024-01-05 | GSE252114 | GEO

Human blastoids model blastocyst development and implantation

Project description:About one week after fertilization, human embryos implant into the uterus. This necessitates the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (PXGL hPSCs) efficiently (>70%) form blastoids generating blastocyst-stage analogs of the 3 founding lineages (>97% trophectoderm, epiblast, and primitive endoderm) according to the sequence and to the pace of blastocyst development. Blastoids form the first axis and we observe that the epiblast induces the maturation of the polar trophectoderm that consequently acquires the specific and transient potential to attach to hormonally-stimulated endometrial cells. Such human blastoids are faithful, scalable, versatile, and ethical models to explore human implantation and development.

2021-09-15 | GSE177689 | GEO

Bovine blastocyst like structures derived from stem cell cultures

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2023-05-16 | GSE221248 | GEO

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

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2019-10-17 | GSE135701 | GEO

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