ScRNA-seq of HSCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE203129 | GEO | 2023/05/16
REPOSITORIES: GEO
Similar Datasets
Project description:Both mHSCs and nHSCs had activated differentiation genes upon LM challenge; however, mHSCs more robustly increased cell cycle and T lymphocyte-differentiation genes but reduced myeloid-, erythrocyte- and B cell-differentiation genes compared to nHSCs upon LM challenge
2024-05-02 | GSE202099 | GEO
Project description:Both mHSCs and nHSCs had activated differentiation genes upon LM challenge; however, mHSCs more robustly increased cell cycle and T lymphocyte-differentiation genes but reduced myeloid-, erythrocyte- and B cell-differentiation genes compared to nHSCs upon LM challenge
2024-05-02 | GSE202142 | GEO
Project description:Alcoholic liver disease (ALD) is a leading cause of cirrhosis in the United States, which is characterized by extensive deposition of extracellular matrix proteins (ECM) and formation of a fibrous scar. Hepatic Stellate Cells (HSCs) are the major source of Collagen Type I producing myofibroblasts in ALD fibrosis. However, the mechanism of alcohol-induced activation of human and mouse HSCs is not fully understood. We compared the gene expression profiles of primary cultured human HSCs (hHSCs) isolated from patients with ALD (n=3) or without underlying liver disease (n=4) using RNA-Seq analysis. Furthermore, the gene expression profile of ALD hHSCs was compared to that of alcohol-activated mHSCs (isolated from intragastric (IG) alcohol-fed mice), or carbon-tetrachloride (CCl4)-activated mouse HSCs (mHSCs). Comparative transcriptome analysis revealed that ALD hHSCs, and alcohol- and CCl4-activated mHSCs share the expression of common HSC activation (Col1a1, Acta1, PAI-1, TIMP1, LOXL2), indicating that a common mechanism underlies activation of human and mouse HSCs. Furthermore, alcohol-activated mHSCs most closely recapitulate the gene expression profile of ALD hHSCs. We identified the genes that are similarly and uniquely upregulated in primary cultured alcohol-activated hHSCs and freshly isolated mHSCs, which include CSF1R, PLEK, LAPTM5, CD74, CD53, MMP9, CD14, CTSS, TYROBP, ITGB2, and other genes (compared to CCl4-activated mHSCs). We identified genes in alcohol-activated mHSCs from IG alcohol-fed mice that are largely consistent with the gene expression profile of primary cultured hHSCs from ALD patients. These genes are unique to alcohol-induced HSC activation in two species, and therefore, may become new targets or readout for anti-fibrotic therapy in experimental models of ALD.
2020-04-10 | GSE141100 | GEO
Project description:Histone deacetylase (HDAC) inhibitors are widely utilized in hematopoietic malignance therapy; nevertheless, little is currently known concerning their effects on normal myelopoiesis. In order to investigate a putative interference of HDAC inhibitors in myeloid commitment of hematopoietic stem/progenitor cells (HSPCs) we treated CD34+ cells with valproic acid (VPA). Moreover, we investigate changes in gene expression induced by VPA treatment on HSPCs, by means of microarray analysis in VPA treated and untreated (CTR) CD34+ cells. VPA treatment induced H4 histone acetylation in CD34+ cells and blocked them in G0-G1 phase of cell cycle. CD34 expression is maintained for a longer time in VPA treated cells, while the physiological decrease of CD34 antigen occurred in CTR cells. Moreover, VPA favored erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage lineages, as demonstrated by immunophenotyping, morphological and clonogenic analysis. Finally, we demonstrated that VPA up-regulated master gene regulators of erythrocyte and megakaryocyte differentiation (GFI1B and MLLT3) through histone iper-acetylation of their promoters. These results indicate that VPA treatment enhances erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage one. Microarray data provide for the first time a detailed molecular support for the biological effects promoted by VPA treatment in HSPCs. Human CD34+ cells were purified from umbilical Cord Blood (CB) samples. After an initial 24 hours of incubation, CD34+ cells were exposed to VPA. Total cellular RNA was extracted from untreated (CTR) and VPA treated CD34+ HSCs after 48 hours of treatment.
2013-04-11 | E-GEOD-31283 | biostudies-arrayexpress
Project description:Histone deacetylase (HDAC) inhibitors are widely utilized in hematopoietic malignance therapy; nevertheless, little is currently known concerning their effects on normal myelopoiesis. In order to investigate a putative interference of HDAC inhibitors in myeloid commitment of hematopoietic stem/progenitor cells (HSPCs) we treated CD34+ cells with valproic acid (VPA). Moreover, we investigate changes in gene expression induced by VPA treatment on HSPCs, by means of microarray analysis in VPA treated and untreated (CTR) CD34+ cells. VPA treatment induced H4 histone acetylation in CD34+ cells and blocked them in G0-G1 phase of cell cycle. CD34 expression is maintained for a longer time in VPA treated cells, while the physiological decrease of CD34 antigen occurred in CTR cells. Moreover, VPA favored erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage lineages, as demonstrated by immunophenotyping, morphological and clonogenic analysis. Finally, we demonstrated that VPA up-regulated master gene regulators of erythrocyte and megakaryocyte differentiation (GFI1B and MLLT3) through histone iper-acetylation of their promoters. These results indicate that VPA treatment enhances erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage one. Microarray data provide for the first time a detailed molecular support for the biological effects promoted by VPA treatment in HSPCs.
2013-04-11 | GSE31283 | GEO
Project description:To investigate the molecular mechanism of Uhrf1 in controlling the self-renewal versus differentiation of FL-HSCs, high-throughput sequencing was performed to analyze the transcriptomes of WT and Uhrf1-deficient FL-HSCs.Consistent with the erythroid-biased differentiation of Uhrf1-deficient FL-HSCs, genes involved in erythrocyte differentiation were significantly enriched in Uhrf1-deficient FL-HSCs according to the Gene Ontology (GO) enrichment analysis. We generated gene signatures specific for stemness of HSCs (stem signature) or myeloerythroid progenitors (MEP signature) by subtracting the genes expressed in WT HPC(LK)s from those expressed in WT FL-HSCs or vice versa. Of the stem signature genes, 71.28% showed lower expression and 28.72% showed higher expression in Uhrf1-deficient FL-HSCs compared with WT FL-HSCs. Interestingly, among the MEP signature genes, genes enriched in erythroid differentiation (27.54%) were up-regulated in the absence of Uhrf1, whereas the remaining genes enriched in myeloid-specific genes (72.46%) were suppressed consistent with previous research. Particularly, in comparison to the WT control, Uhrf1-deficient FL-HSCs up-regulated certain erythrocyte differentiation-related genes (e.g., Gata1, Gata2, Gfi1b, Car1, Zfpm1 and Itga2b), most of which were physiologically up-regulated in HPC(LK)s, whereas some genes (Id2, Satb1, Hmga2) that play critical roles in HSC maintenance were down-regulated. These results suggested that Uhrf1 controls the self-renewal versus differentiation of FL-HSCs by suppressing the expression of the erythroid-specific genes and maintaining the expression of HSC stemness genes.
2016-11-30 | GSE85450 | GEO
Project description:Histone modifications have been implicated in stem cell maintenance and differentiation. We have analyzed genome-wide changes in gene expression and histone modifications during differentiation of multipotent human primary hematopoietic stem cells/progenitor cells (HSCs/HPCs) into erythrocyte precursors. Our data indicate that H3K4me1, H3K9me1, and H3K27me1 associate with enhancers of differentiation genes prior to their activation and correlate with basal expression, suggesting that these monomethylations are involved in the maintenance of activation potential required for differentiation. In addition, although the majority of genes associated with both H3K4me3 and H3K27me3 in HSCs/HPCs become silent and lose H3K4me3 after differentiation, those that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1, H4K20me1, and RNA polymerase II in HSCs/HPCs. Thus, our data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification. Genome-wide analysis of 8 histone methylations, H2AZ, and RNA Polymerase II in human CD133+ and CD36+ cells. (20 samples in total) and global change in gene expression in human CD133+ and CD36+ cells. (4 samples in total)
2009-01-09 | E-GEOD-12646 | biostudies-arrayexpress
Project description:Histone modifications have been implicated in stem cell maintenance and differentiation. We have analyzed genome-wide changes in gene expression and histone modifications during differentiation of multipotent human primary hematopoietic stem cells/progenitor cells (HSCs/HPCs) into erythrocyte precursors. Our data indicate that H3K4me1, H3K9me1, and H3K27me1 associate with enhancers of differentiation genes prior to their activation and correlate with basal expression, suggesting that these monomethylations are involved in the maintenance of activation potential required for differentiation. In addition, although the majority of genes associated with both H3K4me3 and H3K27me3 in HSCs/HPCs become silent and lose H3K4me3 after differentiation, those that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1, H4K20me1, and RNA polymerase II in HSCs/HPCs. Thus, our data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification.
2009-01-09 | GSE12646 | GEO
Project description:Uterine leiomyomas (LM) affect up to 80% of all reproductive-age women. LM growth requires progesterone, progesterone receptor (PGR), and the maintenance and proliferation of a small (5%) stem cell population. Stem cell activation and differentiation are driven by DNA methylation and nuclear hormone receptor action, but crosstalk between these mechanisms remains unclear. We performed an integrated analysis of the transcriptome and epigenetic landscape of LM cells at three differentiation stages and the PGR cistrome of whole LM tissue. The PGR-deficient stem cell population harbored a unique methylation landscape, with hypermethylation at the PGR gene locus and PGR-binding regions, which suppressed stem cell responsiveness to progesterone. The DNA methylation inhibitor 5’-Aza upregulated the expression of PGR and its target genes by stimulating PGR recruitment to the targeted gene loci, and significantly depleted the LM stem cell population and its tumor-initiating capacity. We herein provided mechanistic insights via therapeutically accelerating the stem cell differentiation process of a hormone-sensitive tumor.
2020-10-01 | GSE138047 | GEO