Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of quiescent adult liver stem cells and downstream lineages [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE64292 | GEO | 2018/10/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Characterization of quiescent adult liver stem cells and downstream lineages [Agilent Array]

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

The Quantitative Analysis of Transcriptomes Derived From Ezh2- or Ezh1/2-Deleted Leukemia Stem Cells of Murine Acute Myloid Leukemia

Project description:We report dual genetic delstion of Ezh1/2 in murine AML model induced cell cyle progression of quiescent LSCs and cell differentiation of LSCs. To investigate the underlying mechanism by which Ezh1/2 regulate quiescent LSCs and maintein the stemness of LSCs, we performed RNA sequencing of L-GMPs derived from Ezh2- and Ezh1/2-deleted AML mice.

2017-03-11 | GSE96061 | GEO

Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing

Project description:Stem cells (SCs) are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. It was several decades ago, when limbal epithelial SCs (LSCs) that regenerate the corneal epithelium were among the first sporadic, quiescent SCs ever discovered. However, LSC dynamics, heterogeneity and genetic signature are largely unknown. Moreover, recent accumulating evidence strongly suggested that epithelial SCs are actually abundant, frequently dividing cells that display stochastic behavior. In this work, we combined single-cell RNA sequencing and advanced quantitative lineage tracing for in-depth analysis of the murine limbal epithelium. The generated data provides an atlas of cell states of the entire corneal epithelial lineage and reveales the co-existence of two novel LSC populations that reside in separate and well-defined sub-compartments. In the “outer” limbus, we discovered a primitive widespread population of quiescent LSCs (qLSCs) that uniformly express Krt15/Gpha2/Ifitm3/Cd63 proteins that serve as SC reservoire and in boundary formation. In the “inner” peri-corneal limbus, we identified prevalent active LSCs (aLSCs) that express Krt15-GFP/Atf3/Mt1-2/Socs3 and maintain homeostasis. We propose that these SC populations are abundant, follow stochastic rules and neutral drift dynamics. Notably, we provide evidence that T cells serve as niche cells for qLSCs, regulating quiescence and wound response. Taken together, we propose that divergent regenerative strategies are tailored to properly support tissue specific physiological constraints.

2021-03-02 | GSE167992 | GEO

Microarray data of human MLLr AML cells with or without CD93 expression

Project description:Leukemia stem cells (LSCs) share several crucial properties with hematopoietic stem cells (HSCs) including self-renewal, cell cycle quiescence, and expression of a CD34+CD38- immunophenotype, which complicates efforts to eradicate AML by therapeutically targeting LSCs without adversely affecting HSCs. Here we report that CD93, a C-type lectin transmembrane receptor, is preferentially expressed on the cell surface of LSCs compared with HSCs in the genetic subtype of AML with genomic rearrangements of the MLL gene. LSCs that selectively express CD93 are actively cycling, and highly enriched for xeno-engraftment potential, yet comprise a minor component of an otherwise quiescent CD34+CD38- compartment of human AML. Notably, CD93 is required for LSC function in MLL leukemogenesis, and is not simply a passive surface marker co-expressed on LSCs. Thus, CD93 selectively marks and essentially maintains LSCs, and identifies them as predominantly cycling, non-quiescent leukemia-initiating cells in MLL-rearranged AML.

2015-10-02 | GSE64776 | GEO

Intraepithelial papillary neoplasia in the biliary tree is mediated by FGF10 signal

Project description:The new concept of neoplastic lesion of biliary tree, Biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), as a conunterpart of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN), have been reported to be precancerous lesions in hilar and extrahepatic cholangiocarcinoma and arise from lining bile duct epithelium and peribiliary gland (PBG) under inflammation microenvironment in human. However, mouse model is lacking different from intrahepatic cholangiocarcinoma arised from canal of Hering in the liver. In a Doxycyclin-controlled transgenic mouse model of BilIN and IPNB, overexpression of Fibroblast Growth Factor 10 (FGF10) phenocopies human pathology with mutistep progression of cholangiocarcinogenesis in chronic cholangitis. The development and branching morphogenesis of BilIN and IPNB was induced by Fgf10/Erk signal and inhibited by MEK inhibiter. Pdx1+ PBG cells present in IPNB were able to lineage trace the early IPNB lesion as well as Krt19+ cholangiocytes. BiliN and IPNB with Kras mutation was irreversible different from no Kras mutation, and loss of p16 contributed to malignant transformation of BilIN and IPNB. Our data challenge the common paradigms regarding the pathogenesis of BilIN and IPNB.

2019-11-12 | GSE119227 | GEO

RNA-Seq analysis of LT-HSC isolated from fetal liver and adult bone marrow.

Project description:Hematopoietic stem cells (HSC) has unique characteristic to self-renew and replenish the entire blood system. During development, HSCs originate in the aorta-gonads-mesonephros (AGM), from where they migrate into the fetal liver at E11. Once resided in fetal liver HSC proliferate extensively to make sufficient stem pool for adult life. Around birth, HSC from FL migrate to bone marrow (BM) which is major site of hematopoiesis for whole adult life. In contrast to FL HSC, BM HSC remain quiescence state and give rise to different blood cell type under normal homeostatic condition. It has shown that FL HSCs display significantly faster expansion kinetics when transplanted into lethally irradiate mice, compared with HSCs from adult BM. However, detail molecular mechanism behind the difference in self-renewal potential is not fully understood. Here, we present the genome-wide transcriptome analysis of more proliferative FL HSC compared to quiescent BM HSC using RNA-Seq platform.

2016-02-19 | E-MTAB-4034 | biostudies-arrayexpress

RNA sequencing based comparative analysis of human hepatic progenitor cells and their niche from alcoholic steatohepatitis livers

Project description:Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering, that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible for proliferation and differentiation of human HPCs are still poorly understood and the role of HPCs in ASH development is unknown. In this study, we aimed to characterise human HPCs and their interactions with other cells through comparison, on both protein and RNA level, of HPC-enriched cell populations from adult human liver tissue using different isolation methods. Fresh human liver tissue was collected from ASH explant livers and HPC-enriched cell populations were obtained via three different isolation methods: side population (SP), EpCAM and TROP-2 membrane marker isolation. Gene expression profiles of fluorescent activated cell sorted HPCs, whole liver extracts and laser microdissected HPC niches were determined by RNA sequencing. Immunohistochemical evaluation of the isolated populations indicated the enrichment of HPCs in the SP, EpCAM+ and TROP-2+ cell populations. Pathway analysis of the transcription profiles of human HPCs showed an enrichment and activation of known HPC pathways like Wnt/β-catenin, TWEAK and HGF. Integration of the HPC niche profile suggests autocrine signalling by HPCs (TNF, PDGFB and VEGFA) as well as paracrine signalling from the surrounding niche cells including MIF and IGF-1. In addition, we identified IL-17A signalling as a potentially novel pathway in HPC biology. In conclusion, we provide the first RNA-seq based, comparative transcriptome analysis of isolated human HPCs from ASH patients and revealed active signalling between HPCs and their surrounding niche cells in ASH livers and suggest that HPCs can actively contribute to liver inflammation.

2019-07-05 | GSE102683 | GEO

Single-cell analysis reveals alterations in limbal stem cells and niche regulations during cornea wound healing

Project description:The rapid and effective regeneration of corneal epithelial cells depends on limbal stem cells (LSCs). The LSCs of mouse can be subdivided into quiescent LSCs (located on the outer limbus, qLSCs) and active LSCs (located on the inner limbus, aLSCs). Here, we used single-cell RNA sequencing to decipher the transcriptional changes in qLSCs and aLSCs and their niche regulations during the corneal wound healing, and reconstructed the pseudotime trajectory and differentiation of LSCs. Our comparative study identified a transcription factor Creb5, expressed in LSCs, that was significantly upregulated after corneal epithelial injury, and the loss-of-function experiments revealed that silencing Creb5 delayed the corneal epithelial healing. Besides, we predicted a significant increase in the number of ligand-receptor pairs for intercellular communications during corneal epithelial wound healing, especially between immune cells and LSCs, implying the participation of various niche cells in limbal stem cell kinetics during corneal epithelial regeneration. Overall, our research reveals numerous findings on the behavior and functionality of LSCs during corneal wound healing, providing reference for the discovery of mechanisms and potential clinical interventions of ocular surface reconstruction.

2024-07-10 | GSE247392 | GEO

Cell quiescence and reprogramming are distinctive features of pre-leukemic stem cells [H2Bgfp]

Project description:The leukemic stem cell concept is well established in B-acute lymphoblastic leukemia (B-ALL). However, the question of how a primary oncogene reprograms stem cell-like properties in committed B-cells and leads to a pre-neoplastic population remains unclear. Here, we used the PAX5-ELN oncogenic model to demonstrate a causal link between the differentiation blockade, the self-renewal and the emergence of pre-leukemic stem cells (pre-LSCs). Through multi-parametric immunophenotyping, we show that PAX5-ELN oncoprotein disrupts the differentiation of pre-leukemic cells by enforcing the IL7r/JAK-STAT signaling pathway. This disruption is associated with the induction of rare and quiescent pre-LSCs that sustain the leukemia-initiating activity, as assessed using the H2B-GFP model. Integration of transcriptomic and chromatin accessibility data reveals that those quiescent pre-LSCs lose B-cell identity and reactivate an immature molecular program, reminiscent of human B-ALL chemo-resistant cells. Collectively, our study sheds new lights on the biological mechanisms underlying the cell-of-origin of leukemia. We performed gene expression profiling analysis using data obtained from RNA-seq of quiescent or proliferative B-cells PEtg mice.

2023-11-01 | GSE210925 | GEO

Cell quiescence and reprogramming are distinctive features of pre-leukemic stem cells [RNA-seq CTV]

2023-11-01 | GSE210924 | GEO