Chemically Induced CD24+ hepatocyte-derived liver progenitor-like cells revert chronic hepatic dysfunction
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ABSTRACT:
PROVIDER: PRJNA515216 | ENA |
REPOSITORIES: ENA
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Project description: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.
2019-07-01 | GSE125095 | GEO
Project description:Here, we chemically induced hepatocyte-like cells (CiHeps) from mouse fibroblasts using a new protocol. To compare the transcriptional profiles between different cocktail-induced cells and primary hepatocytes (pHeps), we profiled the transcriptomes of induced cells and freshly isolated primary mouse hepatocytes. CiHeps' function and maturation-related gene expression was validated as well as the similarity it shares with pHeps.
2022-08-09 | GSE210709 | GEO
Project description:Here, we chemically induced hepatocyte-like cells (CiHeps) from mouse embryonic fibroblasts (MEFs) using a new protocol. To illustrate the transcriptomic landscape of hepatocyte cell formation by chemical induction, scRNA-seq was performed in C6F5UE-C6F(L)V-induced MEFs at 60 days of induction. The analysis of scRNA-seq data revealed that gastrointestinal-like and keratinocyte-like cells were induced along with CiHeps and these induced epithelial cells closely resembled that of their primary counterparts.
2022-08-09 | GSE210710 | GEO
Project description:Expression profiling of CD24+ and CD24- population cells from myeloma cell lines. Results provide insight into the role of CD24+ cells in myeloma development. Keywords: multiple myeloma, cancer stem cell, CD24
2020-10-31 | GSE109650 | GEO
Project description:CD24+ and CD24- myeloma-derived cancer stem cell lines
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Project description:Being involved in adhesion, migration, and invasion, the highly glycosylated signal transducer CD24 (cluster of differentiation 24) has been implicated to play an essential role during carcinogenesis. Previously, the molecular and (epi)genetic regulation of CD24 has been characterized in testicular germ cell tumors (GCT). Here, CD24 was exclusively found in embryonal carcinoma (EC), which represents the stem cell like population of GCT (see project PXD025110). For a better understanding of the molecular function of CD24, this study aimed at the identification of the direct interaction partners of CD24 not only in GCTs, but also in other urologic malignancies, such as urothelial- (UC), prostate- (PC), and renal cell carcinoma (RCC). For this purpose, co-immunoprecipitations of CD24 were performed in GCT, UC, PC, and RCC cell lines, while CD24-deficient EC cells as well as IgG2a controls were included for high validity. Extracted proteome was measured by liquid-chromatography coupled with mass spectrometry (LS-MS).
2023-05-10 | PXD039063 | Pride
Project description:Liver fibrosis is a strong predictor of long-term mortality in patients with non-alcoholic fatty liver disease; yet the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely under-stood. Using a cell type-resolved genomics approach, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a partial loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a net-work of NASH-activated transcription factors (TFs), as exemplified by Elf3 and Glis2. Indeed, Elf3 and Glis2 controlled hepatocyte identity and fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell (HSC) gene programs. Thus, interconnected TF networks not only promoted hepatocyte dysfunction, but also directed the intra-hepatic crosstalk with HSCs necessary for NASH and fibrosis progression implying molecular “hub-centered” targeting strategies to be superior to existing mono-target approaches as currently used in NASH therapy.
2021-07-13 | PXD025691 | Pride
Project description:Gene expression were identified with or without CD24 gene silencing in Du145 cells. RNA isolated from 5 independent cultures of Scramble control, 3 cultures of CD24-ShRNA1 and 2 cultures of CD24-ShRNA2 were tested using Affimatrx Human U133 Plus 2.0 microarrays.
2014-05-05 | E-GEOD-46708 | biostudies-arrayexpress
Project description:Background & Aims: Obesity is the most important risk factor and a potential treatment target for fatty liver disease (FLD). The continuous adaptation or ‘remodelling’ of hepatic mitochondrial flexibility plays a key role in the pathogenesis of FLD. Human adipose stem cell (hASC)-derived hepatocyte-like cells (HLCs) offer attractive tools for the research and therapy of liver dysfunction. However, evidence showing the ‘remodelling’ of hepatic mitochondrial flexibility or differentiation capability of hASCs in obese patients is lacking. Methods: The differentiation capability and mitochondrial structure and function of hepatic cells were evaluated by measuring gene expression, de novo lipogenesis and mitochondrial respiration in HLCs derived from hASCs of obese patients and lean controls. The ability of the GSK3 inhibitor CHIR-99021 to modify the mitochondrial oxidative dysfunction was evaluated in the HLCs derived from the hASCs of obese patients. Results: hASCs from obese patients showed the potential to differentiate into HLCs. HLCs from the hASCs of obese patients exhibited the characteristics of hepatic steatosis, lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, and the basal oxygen consumption rate of the HLCs derived from the hASCs of obese patients by upregulating the expression of PGC-1α, the transcription factor involved in mitochondrial biogenesis and ‘remodelling’. Conclusions: The results demonstrate that obese patient ASC-derived HLCs had mitochondrial oxidative dysfunction, which may represent the consequence of hepatic steatosis.
2021-03-19 | GSE151760 | GEO
Project description:Expression data from WT CD24+CD172a+ cDC2s, WT CD24–CD172+ cDC2s, and WT CD24+CD172a– cDC1s
| PRJNA548944 | ENA