Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA382725 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5521460_1.fastq.gz | Fastqsanger.gz | |||
| SRR5521460_2.fastq.gz | Fastqsanger.gz | |||
| SRR5521470_1.fastq.gz | Fastqsanger.gz | |||
| SRR5521470_2.fastq.gz | Fastqsanger.gz | |||
| SRR5521480_1.fastq.gz | Fastqsanger.gz |
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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: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.
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Project description:Fibroblasts can be chemically induced to pluripotent stem cells (CiPSCs) through an extraembryonic endoderm (XEN)-like state or directly converted into other differentiated cell lineages. However, the mechanisms underlying chemically-induced cell fate reprogramming remain unclear. Here, a transcriptome-based screen of biologically active compounds uncovered that CDK8 inhibition was essential to enable chemically-induced reprogramming from fibroblasts into XEN-like cells, then CiPSCs. RNA-seq analysis showed that a CDK8 inhibitor, MSC2530818, inhibited pro-inflammatory pathways that suppress chemical reprogramming, and facilitated the induction of a multi-lineage priming state, indicating the establishment of plasticity in fibroblasts. CDK8 inhibition also resulted in chromatin accessibility profile and Pol II occupation profile similar to that under initial chemical reprogramming. Moreover, CDK8 inhibition greatly promoted transgene-mediated reprogramming of mouse fibroblasts into hepatocyte-like cells, and chemical reprogramming of human fibroblasts into adipocytes. These collective findings thus define CDK8 as a general molecular barrier in multiple cell reprogramming processes, and as a common target for inducing plasticity and cell fate conversion.
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Project description:Fibroblasts can be chemically induced to pluripotent stem cells (CiPSCs) through an extraembryonic endoderm (XEN)-like state or directly converted into other differentiated cell lineages. However, the mechanisms underlying chemically-induced cell fate reprogramming remain unclear. Here, a transcriptome-based screen of biologically active compounds uncovered that CDK8 inhibition was essential to enable chemically-induced reprogramming from fibroblasts into XEN-like cells, then CiPSCs. RNA-seq analysis showed that a CDK8 inhibitor, MSC2530818, inhibited pro-inflammatory pathways that suppress chemical reprogramming, and facilitated the induction of a multi-lineage priming state, indicating the establishment of plasticity in fibroblasts. CDK8 inhibition also resulted in chromatin accessibility profile and Pol II occupation profile similar to that under initial chemical reprogramming. Moreover, CDK8 inhibition greatly promoted transgene-mediated reprogramming of mouse fibroblasts into hepatocyte-like cells, and chemical reprogramming of human fibroblasts into adipocytes. These collective findings thus define CDK8 as a general molecular barrier in multiple cell reprogramming processes, and as a common target for inducing plasticity and cell fate conversion.
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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: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.
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