Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297459 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2541730_1.fastq.gz | Fastqsanger.gz | |||
| SRR2541730_2.fastq.gz | Fastqsanger.gz | |||
| SRR2541740_1.fastq.gz | Fastqsanger.gz | |||
| SRR2541740_2.fastq.gz | Fastqsanger.gz | |||
| SRR2541731_1.fastq.gz | Fastqsanger.gz |
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Project description:Pluripotent stem cells can be generated from somatic cells by using pure chemicals.However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. In this study, we found that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to CiPSCs, a new route that differs from the pathway of transcription factor-induced reprogramming. Moreover, by more precisely manipulating the cell fate transition in a step-wise manner through the XEN-like state, we identified small-molecule boosters and established a robust chemical reprogramming system, with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a unique and promising approach in the future manipulation of cell fates. We analyzed the gene expression profiles of intermediate cells obtained from diferent timepoints during chemical reprogramming process,using RNA-Sequencing. Embryo-derived XEN cells (eXENs), chemically-derived eXEN cell lines (CeXENs), embryonic stem cells (ESCs) and chemically-induced pluripotent stem cells (CiPSCs) are used as controls.
2015-12-09 | E-GEOD-73631 | biostudies-arrayexpress
Project description:Somatic cells can be chemically reprogrammed into a pluripotent stem cell (CiPSC) state, mediated by an extraembryonic endoderm- (XEN-) like state. We found that the chemical cocktail applied in CiPSC generation initially activated a plastic state in mouse fibroblasts before transitioning into XEN-like cells. The plastic state was characterized by broadly activated expression of development-associated transcription factors (TFs), such as Sox17, Ascl1, Tbx3, and Nkx6-1, with a more accessible chromatin state indicating an enhanced capability of cell fate conversion. Intriguingly, introducing such a plastic state remarkably improved the efficiency of chemical reprogramming from fibroblasts to functional neuron-like cells with electrophysiological activity or beating skeletal muscles. Furthermore, the generation of chemically induced neuron-like cells or skeletal muscles from mouse fibroblasts was independent of the intermediate XEN-like state or the pluripotency state. In summary, our findings revealed a plastic chemically activated multi-lineage priming (CaMP) state at the onset of chemical reprogramming. This state enhanced the cells’ potential to adapt to other cell fates. It provides a general approach to empowering chemical reprogramming methods to obtain functional cell types bypassing inducing pluripotent stem cells.
2022-03-17 | GSE155818 | GEO
Project description:Pluripotent stem cells can be generated from somatic cells by using pure chemicals.However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. In this study, we found that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to CiPSCs, a new route that differs from the pathway of transcription factor-induced reprogramming. Moreover, by more precisely manipulating the cell fate transition in a step-wise manner through the XEN-like state, we identified small-molecule boosters and established a robust chemical reprogramming system, with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a unique and promising approach in the future manipulation of cell fates.
2015-12-09 | GSE73631 | GEO
Project description:Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state. We find that Sox17 is initially activated by the chemical cocktails, and XEN cell fate specialization is subsequently mediated by Sox17 activated expression of other XEN master genes, such as Sall4 and Gata4. Furthermore, this stepwise process is differentially regulated. The core reprogramming chemicals CHIR99021, 616452 and Forskolin are all necessary for Sox17 activation, while differently required for Gata4 and Sall4 expression. The addition of chemical boosters in different phases further improves the generation efficiency of XEN-like cells. Taken together, our work demonstrates that chemical reprogramming is regulated in 3 distinct “prime–specify–transit” phases initiated with endogenous Sox17 activation, providing a new framework to understand cell fate determination.
2020-11-05 | GSE144097 | GEO
Project description:We profile 36,199 single-cell transcriptomes at multiple timepoints throughout a highly efficient chemical reprogramming system using RNA-sequencing and reconstruct their progression trajectories. Through identifying sequential molecular events, we reveal that the dynamic early embryonic-like programs account for successful reprogramming from XEN-like state to pluripotency, including the transcriptomic signature of concomitant two-cell (2C) embryonic-like and early pluripotency program and the epigenetic signature of notable genome-wide DNA demethylation.
2018-06-24 | GSE114952 | GEO
Project description:While the reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, they also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established alongside the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. Several studies have shown that endodermal genes are upregulated in fibroblasts undergoing reprogramming, although whether endodermal genes promote or inhibit acquisition of pluripotency is unclear. We show that, in fibroblasts undergoing conventional reprogramming, OSKM-induced expression of endodermal genes leads to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to iPS cells, indicating that OSKM are sufficient to drive cells to two distinct fates during reprogramming. Sequence-based mRNA transcriptional profiling of three different cell lines (MEF, XEN, iXEN) with multiple biological replicates, under two different growth medium conditions (ESC medium, XEN medium) for XEN and iXEN cells.
2016-03-03 | E-GEOD-77550 | biostudies-arrayexpress
Project description:During development, progenitors of embryonic stem (ES) and extraembryonic endoderm stem (XEN) cells are concomitantly specified within the inner cell mass (ICM) of the mouse blastocyst. Similarly, XEN cells are induced (iXEN cells) alongside induced pluripotent stem (iPS) cells following overexpression ofOct4,Sox2,Klf4andMyc(OSKM) during somatic cell reprogramming. It is unclear how or why this cocktail produces both stem cell types, but OCT4 has been associated with non-pluripotent outcomes. In this report, we show that, during OSKM reprogramming, many individualOct4-GFP-expressing cells are fated to become iXEN cells. Interestingly, SKM alone was also sufficient to induce iXEN cell formation, likely via activation of endogenousOct4.These observations indicate that iXEN cell formation is not strictly an artifact ofOct4overexpression. Moreover, our results suggest that a pathway to XEN may be an integral feature of establishing pluripotency during reprogramming, as in early embryo development.
2024-02-15 | GSE244818 | GEO
Project description:Small-molecule based lineage reprogramming has newly emerged as a promising approach for generating functional cell types. We recently found that the chemical induction of iPSCs from fibroblasts pass through an extra-embryonic endoderm (XEN)-like state. In this study, we demonstrated that these chemically-induced XEN-like cells were not restricted to be reprogrammed to iPSCs, but feasible to be induced into functional neurons, bypassing the pluripotent stage. These induced neurons possessed neuron-specific expression profiles, formed functional synapses in culture dish and further matured after transplantation into brains of adult mice. Notably, by using similar principles, hepatocytes could also be induced from the XEN-like cells. Furthermore, the XEN-like cells are highly expandable (for at least 20 passages), retaining genome stability and lineage specifying potentials. Our study establishes a featured route of chemical lineage reprogramming and may provide a universal platform for generating large amounts of diverse functional cell types via the expandable XEN-like state.
2017-06-28 | GSE97721 | GEO
Project description:Reprogramming to pluripotency through a somatic stem cell intermediate
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Project description:Deterministic direct reprogramming of somatic cells to pluripotency [RRBS]
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