Kinetics of chromatin structures during hepatic conversion [Hi-C]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA625936 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11561403_1.fastq.gz | Fastqsanger.gz | |||
| SRR11561403_2.fastq.gz | Fastqsanger.gz | |||
| SRR11561404_1.fastq.gz | Fastqsanger.gz | |||
| SRR11561404_2.fastq.gz | Fastqsanger.gz | |||
| SRR11561405_1.fastq.gz | Fastqsanger.gz |
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Project description:Cell plasticity endows differentiated cells with competence to be reprogrammed to other identities. While reprogramming factors-induced epigenetic changes have been characterized, intrinsic chromatin features underlying cell plasticity remain elusive. By characterizing kinetics of high-order chromatin structures during transdifferentiation from fibroblasts to hepatocytes, we identified contiguous compartment switchable regions (CSRs). Compartment B to A CSRs (B-to-A CSRs), enriched with hepatocyte genes and demarcated by loop anchors, displayed a chimeric status of pre-existing chromatin accessibility in repressive compartment in fibroblasts. Pre-existing accessibility allowed the occupancy of pioneer factor Foxa3 to B-to-A CSRs, triggering compartment switch, H3K27ac gain and H3K27me3 reduction, and hepatocyte gene activation. Moreover, chimeric chromatin status appeared to be related with fibroblasts reprogramming to neurons, cardiomyocytes and pluripotent stem cells. Together, pre-existing accessibility in compartment B defines a chimeric chromatin status that may constitute intrinsic attribute for cell plasticity.
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Project description:Recent studies have shown that defined hepatic factors could lead to the direct conversion of fibroblasts into induced hepatocytes (iHeps). However, reported conversion efficiencies are vey low and the underlying mechanism of the hepatic lineage conversion is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Throughout screening for additional factors that could potentially enhance the kinetics of the MET and hepatic programs, we have found that c-Myc and Klf4 (CK) dramatically accelerate the conversion kinetics, resulting in remarkably improved generation of iHeps (>87 fold). Furthermore, we identified small molecules that could replace the roles of CK and thus led to the highly efficient generation of iHeps without CK. Finally, we show that a single factor (Hnf1α) supported by small molecules is sufficient to robustly induce transprogramming of fibroblasts into functional hepatocyte-like cells with high yield. This novel approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into clinic.
2013-12-03 | GSE52566 | GEO
Project description:Cell plasticity endows differentiated cells with competence to be reprogrammed to other identities. While reprogramming factors-induced epigenetic changes have been characterized, intrinsic chromatin features underlying cell plasticity remain elusive. By characterizing kinetics of high-order chromatin structures during transdifferentiation from fibroblasts to hepatocytes, we identified contiguous compartment switchable regions (CSRs). Compartment B to A CSRs (B-to-A CSRs), enriched with hepatocyte genes and demarcated by loop anchors, displayed a chimeric status of pre-existing chromatin accessibility in repressive compartment in fibroblasts. Pre-existing accessibility allowed the occupancy of pioneer factor Foxa3 to B-to-A CSRs, triggering compartment switch, H3K27ac gain and H3K27me3 reduction, and hepatocyte gene activation. Moreover, chimeric chromatin status appeared to be related with fibroblasts reprogramming to neurons, cardiomyocytes and pluripotent stem cells. Together, pre-existing accessibility in compartment B defines a chimeric chromatin status that may constitute intrinsic attribute for cell plasticity.
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Project description:Cell plasticity endows differentiated cells with competence to be reprogrammed to other identities. While reprogramming factors-induced epigenetic changes have been characterized, intrinsic chromatin features underlying cell plasticity remain elusive. By characterizing kinetics of high-order chromatin structures during transdifferentiation from fibroblasts to hepatocytes, we identified contiguous compartment switchable regions (CSRs). Compartment B to A CSRs (B-to-A CSRs), enriched with hepatocyte genes and demarcated by loop anchors, displayed a chimeric status of pre-existing chromatin accessibility in repressive compartment in fibroblasts. Pre-existing accessibility allowed the occupancy of pioneer factor Foxa3 to B-to-A CSRs, triggering compartment switch, H3K27ac gain and H3K27me3 reduction, and hepatocyte gene activation. Moreover, chimeric chromatin status appeared to be related with fibroblasts reprogramming to neurons, cardiomyocytes and pluripotent stem cells. Together, pre-existing accessibility in compartment B defines a chimeric chromatin status that may constitute intrinsic attribute for cell plasticity.
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Project description:Cell plasticity endows differentiated cells with competence to be reprogrammed to other identities. While reprogramming factors-induced epigenetic changes have been characterized, intrinsic chromatin features underlying cell plasticity remain elusive. By characterizing kinetics of high-order chromatin structures during transdifferentiation from fibroblasts to hepatocytes, we identified contiguous compartment switchable regions (CSRs). Compartment B to A CSRs (B-to-A CSRs), enriched with hepatocyte genes and demarcated by loop anchors, displayed a chimeric status of pre-existing chromatin accessibility in repressive compartment in fibroblasts. Pre-existing accessibility allowed the occupancy of pioneer factor Foxa3 to B-to-A CSRs, triggering compartment switch, H3K27ac gain and H3K27me3 reduction, and hepatocyte gene activation. Moreover, chimeric chromatin status appeared to be related with fibroblasts reprogramming to neurons, cardiomyocytes and pluripotent stem cells. Together, pre-existing accessibility in compartment B defines a chimeric chromatin status that may constitute intrinsic attribute for cell plasticity.
2023-04-17 | GSE148830 | GEO
Project description:Recent studies have shown that defined sets of transcription factors could directly convert fibroblasts into induced hepatocytes (iHeps). However, the underlying mechanism of direct conversion process toward a hepatic lineage is largely unknown. Here, we report that the direct conversion kinetics from fibroblasts into iHeps throughout screening multiple additional factors that potentially rescue the delayed kinetics of MET and hepatic program. Mouse embryonic fibroblasts (MEFs) were efficiently converted into iHeps in the presence of c-Myc and Klf4 (CK), the activators for MET process, with the previously defined sets of hepatic transcription factors, resulting in remarkably improved generation of iHeps. Furthermore, in the presence of CK, Hnf4? alone could convert fibroblasts into iHeps within 5 days with a relatively higher efficiency. Cells transduced with different combinations of factors were cultured in standard Hep medium. Epithelial colonies were observed within 5 days with much higher numbers in the presence of additional factor, c-Myc and Klf4, compared to control group, indicating the number of epithelial colony was dramatically increased in the presence of additional stem cell factors
2013-12-03 | E-GEOD-52566 | biostudies-arrayexpress