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| Status |
Public on Jul 07, 2019 |
| Title |
A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver injury-associated YAP signaling (ATAC-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. The intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed. Here we show that Arid1a, a key component of the SWI/SNF chromatin remodeling complex, controls liver regeneration and gene expression associated with emergence of injury-induced progenitor-like cells (LPLCs). Hepatocyte-specific Arid1a ablation reduces LPLC gene expression in several models of periportal liver injury and impairs liver regeneration, leading to organ dysfunction. Arid1a establishes a permissive chromatin state at LPLC-enriched genes during homeostasis, suggesting it endows hepatocytes with competence to respond to injury-induced signals. Consistently, Arid1a facilitates binding of YAP, a critical regeneration signaling pathway, to LPLC-enriched genes, and Arid1a deletion prevents their YAP-associated induction following injury. Together, these findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration.
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| Overall design |
Normal hepatocytes and DDC-injured hepatocytes were isolated from Arid1a wild type and Arid1a liver specific KO mouse livers by a two-step liver collagenase perfusion and further purified by a series of low speed gravity centrifugation (3x2minx50g). DDC-injured hepatocytes were isolated from Sox9CreERT2:RFP reporter mice by gravity purification, and Sox9+ reprogrammed hepatocytes (LPLCs) were further isolated by sorting RFP+ hepatocytes based on the RFP expression via FACS. Biliary epithelia cells (BECs) were isolated from CK19CreERT2:RFP reporter mice by sorting RFP+ non parenchymal cells based on the RFP expression via FACS. The chromatin accessibility of normal hepatocytes, DDC-injured hepatocytes, LPLCs and BECs were identified via ATAC-seq.
Please note that each processed data .bw file was generated from both replicate samples and is linked to the corresponding Rep1 sample records.
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| Contributor(s) |
Li W, Hui L |
| Citation(s) |
31271748 |
| |
| Submission date |
Mar 07, 2018 |
| Last update date |
Oct 06, 2019 |
| Contact name |
Lijian Hui |
| E-mail(s) |
huilab@sibcb.ac.cn
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| Organization name |
CEMCS, CAS
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| Department |
SIBCB
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| Lab |
Huilab
|
| Street address |
yueyang road 320
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
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| Samples (11)
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| This SubSeries is part of SuperSeries: |
| GSE111502 |
A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver injury-associated YAP signaling |
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| Relations |
| BioProject |
PRJNA437239 |
| SRA |
SRP134083 |
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