Single-cell RNA-seq of hiPSCs under 5iLAF naïve culture conditions
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE197889 | GEO | 2022/11/18
REPOSITORIES: GEO
Similar Datasets
Project description:Single-cell RNA-seq of hiPSCs under 5iLAF naïve culture conditions
| PRJNA812605 | ENA
Project description:Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental studies and therapeutic manipulations. However, the molecular mechanisms involved in establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with 5iLAF naïve induction strategy, we performed integrative analysis across the timeline from human fibroblasts to naïve iPSCs, which reveals ordered expression waves of gene networks sharing signatures with embryonic development process from post-implantation to pre-implantation stages. We also observed a significant transient re-activation of transcripts with 8-cell-stage-like characteristics in late naïve reprogramming stages. Moreover, combined quantitative proteomics analysis with transcriptional dynamics during naïve pluripotency induction, we identified ALPPL2 as the specific surface marker for human naïve pluripotency. Altogether, our study deepens the understanding of molecular mechanisms of human naïve pluripotency.
2018-03-03 | GSE89060 | GEO
Project description:Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental studies and therapeutic manipulations. However, the molecular mechanisms involved in establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with 5iLAF naïve induction strategy, we performed integrative analysis across the timeline from human fibroblasts to naïve iPSCs, which reveals ordered expression waves of gene networks sharing signatures with embryonic development process from post-implantation to pre-implantation stages. We also observed a significant transient re-activation of transcripts with 8-cell-stage-like characteristics in late naïve reprogramming stages. Moreover, combined quantitative proteomics analysis with transcriptional dynamics during naïve pluripotency induction, we identified ALPPL2 as the specific surface marker for human naïve pluripotency. Altogether, our study deepens the understanding of molecular mechanisms of human naïve pluripotency.
2018-03-03 | GSE89058 | GEO
Project description:Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental studies and therapeutic manipulations. However, the molecular mechanisms involved in establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with 5iLAF naïve induction strategy, we performed integrative analysis across the timeline from human fibroblasts to naïve iPSCs, which reveals ordered expression waves of gene networks sharing signatures with embryonic development process from post-implantation to pre-implantation stages. We also observed a significant transient re-activation of transcripts with 8-cell-stage-like characteristics in late naïve reprogramming stages. Moreover, combined quantitative proteomics analysis with transcriptional dynamics during naïve pluripotency induction, we identified ALPPL2 as the specific surface marker for human naïve pluripotency. Altogether, our study deepens the understanding of molecular mechanisms of human naïve pluripotency.
2018-03-03 | GSE89056 | GEO
Project description:The first lineage choice made in human embryo development separates trophectoderm from the inner cell mass, which proceeds to form the pluripotent epiblast and primitive endoderm. Trophectoderm on the other hand gives rise to the placenta. Naïve pluripotent stem cells are derived from the pluripotent epiblast of the blastocyst and offer possibilities to explore how lineage integrity is maintained. Here, we discover that Polycomb repressive complex 2 (PRC2) restricts an intrinsic capacity of naïve pluripotent stem cells to give rise to trophectoderm. Through quantitative epigenome profiling, we find that broad histone H3 lysine 27 trimethylation (H3K27me3) hypermethylation is a common feature of naïve pluripotency across species. We define a previously unappreciated, naïve-specific set of bivalent promoters, featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm transcription factors in a transcriptionally poised state that is resolved to an active state upon depletion of H3K27me3 via inhibition of the enzymatic subunits of PRC2, EZH1/2. Conversely, primed human embryonic stem cells cannot be driven towards trophectoderm development via PRC2 inhibition. While naïve and primed hESCs share the majority of bivalent promoters, PRC2 contributes to the repression of largely non-overlapping subsets of these promoters in each state, hence H3K27me3-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.
2021-08-23 | GSE181242 | GEO
Project description:The first lineage choice made in human embryo development separates trophectoderm from the inner cell mass, which proceeds to form the pluripotent epiblast and primitive endoderm. Trophectoderm on the other hand gives rise to the placenta. Naïve pluripotent stem cells are derived from the pluripotent epiblast of the blastocyst and offer possibilities to explore how lineage integrity is maintained. Here, we discover that Polycomb repressive complex 2 (PRC2) restricts an intrinsic capacity of naïve pluripotent stem cells to give rise to trophectoderm. Through quantitative epigenome profiling, we find that broad histone H3 lysine 27 trimethylation (H3K27me3) hypermethylation is a common feature of naïve pluripotency across species. We define a previously unappreciated, naïve-specific set of bivalent promoters, featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm transcription factors in a transcriptionally poised state that is resolved to an active state upon depletion of H3K27me3 via inhibition of the enzymatic subunits of PRC2, EZH1/2. Conversely, primed human embryonic stem cells cannot be driven towards trophectoderm development via PRC2 inhibition. While naïve and primed hESCs share the majority of bivalent promoters, PRC2 contributes to the repression of largely non-overlapping subsets of these promoters in each state, hence H3K27me3-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.
2021-08-23 | GSE181241 | GEO
Project description:Single-cell RNA-seq reveals that Polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts an intrinsic capacity of pre-implantation pluripotent stem cells to give rise to trophectoderm and mesoderm lineages. Inhibition of PRC2 forces naïve hESC into an ‘activated’ state through which differentiation into either trophectoderm or mesoderm lineages is triggered. This trajectory is distinct from embryonic lineage specification out of the post-implantation pluripotent state, hence PRC2-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.
2022-03-14 | GSE196280 | GEO
Project description:A limited number of accessible and representative models of human trophoblast cells currently exist for disease modeling and improving our understanding of placentation. Current stem cell models involve either a transition through a naïve stem cell fate or precise dynamic control of multiple interacting growth factor and small molecule cues. Here, we show that simple exposure of hiPSCs to two small molecules, retinoic acid (RA) and the Wnt signaling agonist CHIR 99021 (CHIR), results in rapid, synergistic upregulation of CDX2, an important transcription factor for trophectoderm cell induction and maintenance of the trophoblast cell population. RA+CHIR-treated cells have a transcriptional profile with high similarity to that of primary trophectoderm cells, and they can also be further differentiated into cells with features of syncytiotrophoblasts and extravillous trophoblasts. We assessed RA+CHIR-treated cells for the established set of criteria defining a trophectoderm cell model, and the cells possess all of the features necessary to be considered a valid model. Taken together, our data demonstrate the development of a simple method for the generation of functional trophoblast-like cells that can be used to better understand mechanisms and interactions involving the placenta.
2024-08-15 | GSE232692 | GEO
Project description:In primates the amnion emerges through cavitation of the epiblast during implantation, whereas in other species by folding of the ectoderm later around gastrulation. How the mechanisms of amniogenesis diversified in evolution remains unknown. Here we employed the naïve-to-primed transition of human pluripotent stem cells (hPSC) to model peri-implantation epiblast development. We discovered that during this transition hPSC transiently gain the ability to differentiate into cavitating epithelium that transcriptionally matches the early amnion of human embryos. In contrast, primed hPSC produce cells resembling late amnion, uncovering an independent differentiation route. Unexpectedly, single-cell analysis of primate embryos revealed two transcriptionally distinct amniogenesis waves. The early wave occurs through a trophectoderm-like route and encompasses cavitation, whereas the late wave follows an ectoderm-like pathway during gastrulation. The discovery of two independent waves of amniogenesis both of which can be modelled in hPSC explains how amniogenesis through cavitation emerged during the evolution of primates.
2022-04-20 | GSE179309 | GEO
Project description:Little is understood of the molecular mechanisms involved in the earliest cell fate decision in human development, leading to the establishment of the preimplantation embryo’s outer trophectoderm (TE) layer, involved in implantation, while maintaining the inner cell mass (ICM) stem cell population. Using multiple systems biology approaches to compare developmental stages in the early human embryo with single cell transcript data from blastomeres, we have shown that blastomeres considered to be totipotent are not transcriptionally equivalent. Furthermore we have linked the developmental interactome to individual blastomeres and to later cell lineage. This new understanding has clinical implications for understanding the impact of fertility treatments and developmental programming of long term health.
2018-10-15 | GSE110693 | GEO