Characterization of CD63+ adult liver stem cells and downstream lineages
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ABSTRACT:
PROVIDER: PRJNA885442 | ENA |
REPOSITORIES: ENA
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Project description:Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. By employing single-cell RNA-seq technology, we examined transcriptome features of distinct Krt19 lineage-tracing cell types isolated from Krt19CreERT; Rosa26R-GFP reporter mouse livers, and identified adult LSCs, as well as their downstream hepatocytes and cholangiocytes. Importantly, we discovered a novel cell surface LSCs marker, CD63, as well as CD56, which distinguished active and quiescent LSCs. Furthermore, we confirmed that CD63+CD56- quiescent LSCs could be activated by a combined action of VEGF and bFGF, and subsequently underwent terminal differentiation. These findings define an authentic adult liver stem cells compartment and highlight its contribution to liver homeostasis during pathophysiologic processes.
2025-09-01 | GSE214451 | GEO
Project description:Characterization of quiescent adult liver stem cells and downstream lineages
| PRJNA270723 | ENA
Project description:Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. By employing single-cell RNA-seq technology with weighted gene co-expression network analyses (WGCNA), we examined transcriptome features of distinct Krt19 lineage-tracing cell types isolated from Krt19CreERT; Rosa26R-GFP reporter mice, and identified gene expression signatures of quiescent and active adult LSCs, as well as their downstream lineage-restricted progenitors and terminally differentiation hepatocytes and cholangiocytes. Importantly, we discovered a novel cell surface LSC marker, CD63, as well as CD56, which distinguished active and quiescent LSCs. Furthermore, we confirmed that CD63+CD56- quiescent LSCs resided in Canals of Hering and peribiliary glands and that these cells could be activated by a combined action of VEGF and bFGF, and subsequently underwent terminal differentiation. These findings define an authentic adult liver stem cells compartment and highlight its contribution to liver homeostasis during pathophysiologic processes.
2018-10-29 | GSE64292 | GEO
Project description:Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. By employing single-cell RNA-seq technology with weighted gene co-expression network analyses (WGCNA), we examined transcriptome features of distinct Krt19 lineage-tracing cell types isolated from Krt19CreERT; Rosa26R-GFP reporter mice, and identified gene expression signatures of quiescent and active adult LSCs, as well as their downstream lineage-restricted progenitors and terminally differentiation hepatocytes and cholangiocytes. Importantly, we discovered a novel cell surface LSC marker, CD63, as well as CD56, which distinguished active and quiescent LSCs. Furthermore, we confirmed that CD63+CD56- quiescent LSCs resided in Canals of Hering and peribiliary glands and that these cells could be activated by a combined action of VEGF and bFGF, and subsequently underwent terminal differentiation. These findings define an authentic adult liver stem cells compartment and highlight its contribution to liver homeostasis during pathophysiologic processes.
2018-10-29 | GSE64313 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-10-29 | GSE64314 | GEO
Project description:The tetraspanin CD63 is implicated in pro-metastatic signaling pathways, but so far, it is unclear how CD63 levels affect the tumor cell phenotype. Here, we investigated the effect of CD63 modulation in different metastatic tumor cell lines. In vitro, knock down of CD63 induced a more epithelial-like phenotype concomitant with increased E-cadherin expression, downregulation of its repressors Slug and Zeb1, and decreased N-cadherin. In addition, β-catenin protein was markedly reduced, negatively affecting expression of the target genes MMP-2 and PAI-1. β-catenin inhibitors mimicked the epithelial phenotype induced by CD63 knock down. Inhibition of β-catenin upstream regulators PI3K/AKT or GSK3β could rescue the mesenchymal phenotype underlining the importance of the β-catenin pathway in CD63-regulated cell plasticity. CD63 knock down-induced phenotypical changes correlated with a decrease of experimental metastasis, while CD63 overexpression enhanced the tumor cell-intrinsic metastatic potential. Taken together, our data show that CD63 is a crucial player in the regulation of the tumor cell-intrinsic metastatic potential by affecting cell plasticity. Stable knock down of CD63 was performed in SKOV3ipL ovarian carcinoma cell line using 2 shRNAs lentiviral constructs (sh49 and sh51), and as a negative control, a shNT construct. Parental cells, control shNT and the 2 shCD63 cell lines were seeded 24 hours prior to RNA isolation on a 10 cm dish, labelling and hybridization on microarrays. One color experiment with 2 biological replicates of the 4 experimental conditions: SKOV3ipL, SKOV3ipL_shNT, SKOV3ipL_sh49 and SKOV3ipL_sh51.
2015-01-23 | E-GEOD-61957 | biostudies-arrayexpress
Project description:PURPOSE. Building on identification of ABCB5 as a limbal stem cell (LSC) marker, this study evaluates CD63, a newly identified LSC molecule co-expressed with ABCB5, in human limbal epithelial cells to elucidate its role in maintaining corneal epithelial identity. METHODS. RNA sequencing (RNA-seq) was performed on sorted Abcb5-positive and Abcb5-negative murine corneal epithelial cells. CD63 expression in human corneal tissue was assessed by flow cytometry and immunostaining. siRNA-mediated knockdown (KD) of CD63 was conducted in cultured human limbal epithelial cells. Subsequent analyses included qRT-PCR, flow cytometry, RNA-seq, and western blotting. RESULTS. RNA-seq analysis of mouse corneal epithelial cells revealed high expression of LSC markers, including Krt15, Krt6b, Fgfr1, Gpha2, Ifitm3, and Cd63, as well as low expression of differentiation-associated markers, such as Krt12 and Gja1, in Abcb5-positive cells. In human corneal tissue, flow cytometry and immunostaining confirmed robust CD63 expression in the limbal region. siRNA-mediated KD of CD63 in cultured human limbal epithelial cells resulted in a marked reduction in the expression of corneal epithelium-enriched genes, including KRT12, CLU, ALDH1A1, ALDH3A1, TGFBI and MYEOV. Notably, CD63 KD resulted in a ~50 % decrease in expression of a key transcriptional regulator of corneal epithelial identity, PAX6. CONCLUSIONS. CD63 is abundantly expressed in the human limbus and plays a critical role in maintaining the expression of corneal epithelium-specific proteins, likely through modulation of PAX6. These findings underscore the functional significance of CD63 in limbal stem cell biology and its essential contribution to corneal epithelial homeostasis.
2026-03-18 | GSE308189 | GEO
Project description:The tetraspanin CD63 is implicated in pro-metastatic signaling pathways, but so far, it is unclear how CD63 levels affect the tumor cell phenotype. Here, we investigated the effect of CD63 modulation in different metastatic tumor cell lines. In vitro, knock down of CD63 induced a more epithelial-like phenotype concomitant with increased E-cadherin expression, downregulation of its repressors Slug and Zeb1, and decreased N-cadherin. In addition, β-catenin protein was markedly reduced, negatively affecting expression of the target genes MMP-2 and PAI-1. β-catenin inhibitors mimicked the epithelial phenotype induced by CD63 knock down. Inhibition of β-catenin upstream regulators PI3K/AKT or GSK3β could rescue the mesenchymal phenotype underlining the importance of the β-catenin pathway in CD63-regulated cell plasticity. CD63 knock down-induced phenotypical changes correlated with a decrease of experimental metastasis, while CD63 overexpression enhanced the tumor cell-intrinsic metastatic potential. Taken together, our data show that CD63 is a crucial player in the regulation of the tumor cell-intrinsic metastatic potential by affecting cell plasticity.
2015-01-23 | GSE61957 | GEO
Project description:The purpose of this analysis is to analyze the changes in gene expression that occur in cancer cells when CD63 is knocked down in esophageal squamous cell carcinoma (ESCC) cell lines. We performed a comprehensive analysis of mRNA in CD63 knockdown human ESCC cell lines (TE2, TE15) using microarrays.
2024-11-05 | GSE280961 | GEO
Project description:ChIP-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.
| EGAS00001000326 | EGA