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Status |
Public on Jul 01, 2019 |
Title |
Chemically Induced CD24+ hepatocyte-derived liver progenitor-like cells revert chronic hepatic dysfunction |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Administration of soluble molecules to induce endogenous adult liver progenitor-like cells may provide a clinically and effectively applicable approach for liver damage repair. Here, we report that HGF in combination with a cocktail of small molecules Y-27632, A-83-01, and CHIR99021 (HACY), which we have previously defined to convert mature hepatocytes (MHs) to liver progenitor-like cells (HepLPCs) in vitro, could induce the replenishment of endogenous HepLPCs and relieve chronic liver dysfunction during persistent injury. The liver progenitor cells surface marker, CD24, was found to be highly expressed in HepLPCs in vitro. Similarly, injection of HACY into mice with carbon tetrachloride (CCL4) treatment also induced conversion of mature hepatocytes to CD24+ progenitor-like cells in vivo, leading to the attenuation of liver fibrosis. Compared to the liver progenitor cells (LPCs) derived from nonparenchymal cells, HACY-induced CD24+ HepLPCs retained an increased hepatic function by RNA sequencing analysis and could promote restoration of liver function by replacing CCL4-impaired liver cells during chronic hepatic damages. And CD24+ liver stem cells could also be observed in human liver fibrosis tissues and expanded in 3D hepatic spheroid in the present of HACY. Together, the results of our study indicated that injection of a cocktail of HACY might be a valuable multiple targets therapy for patients with chronic liver fibrotic pathologies.
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Overall design |
global expression analysis of RNA sequencing data to compare expression levels of MACS-sorted CD24+ cells from CCL4 and HACY treatment
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Contributor(s) |
Weijian H, Hexin Y |
Citation(s) |
33859762, 37784089 |
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Submission date |
Jan 15, 2019 |
Last update date |
Oct 18, 2023 |
Contact name |
yan hexin |
E-mail(s) |
hexinyw@163.com
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Organization name |
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
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Street address |
No. 1630 East Road
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City |
shanghai |
ZIP/Postal code |
200120 |
Country |
China |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA515216 |
SRA |
SRP179486 |
Supplementary file |
Size |
Download |
File type/resource |
GSE125095_RAW.tar |
640.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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