Single cell RNA sequencing of CD41+ and CD41- CD34+ HPC in model of RUNX1 insufficiency
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166042 | GEO | 2021/05/19
REPOSITORIES: GEO
Similar Datasets
Project description:Single cell RNA sequencing of CD41+ and CD41- CD34+ HPC in model of RUNX1 insufficiency
| PRJNA699017 | ENA
Project description:Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. CHD7 chromatin immunoprecipitation in human CD34+ and mouse HSPCs revealed enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors, and decreased Runx1 occupancy correlated with loss of CHD7 occupancy. CHD7 physically interacts with Runx1 and suppresses Runx1-induced expansion of HSPCs during development, providing both physical and genetic evidence for the Runx1-CHD7 interaction. CHD7 modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
2023-12-01 | GSE84130 | GEO
Project description:The transcription factor Runx1 is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cell (HSPC) pools. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. Here we describe a genome-scale RNAi screen to detect genes that cooperate with Runx1 in regulating HSPCs. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. We show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of HSPCs in vitro. We find an upregulation of HoxA cluster genes upon Pcgf1 knockdown that possibly accounts for the increase in self-renewal. Further, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1 together with the epigenetic repressor Pcgf1 is necessary for terminal differentiation. Thus, our work discovers a genetic link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation. Hematopoietic stem and precursor cells freshly isolated from mice were transduced with an shRNA targeting Pcgf1 or a control shRNA. Cells were selected with puromycin for 36 h before total mRNA was isolated.
2012-06-17 | E-GEOD-33280 | biostudies-arrayexpress
Project description:The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating pre-leukemic stem cells that expand in the bone marrow. Here we show that, counter-intuitively, Runx1 deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involves decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins, and binds the ribosomal DNA repeats. Runx1 deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and endoplasmic reticulum stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1 deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs. Comparison of the phenotypic and molecular properties of normal (Runx1f/f, or WT) versus Runx1 deficient (Mut) hematopoietic stem cells.
2015-07-27 | E-GEOD-67609 | biostudies-arrayexpress
Project description:The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating pre-leukemic stem cells that expand in the bone marrow. Here we show that, counter-intuitively, Runx1 deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involves decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins, and binds the ribosomal DNA repeats. Runx1 deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and endoplasmic reticulum stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1 deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs.
2015-07-27 | GSE67609 | GEO
Project description:Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. CHD7 chromatin immunoprecipitation in human CD34+ and mouse HSPCs revealed enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors, and decreased Runx1 occupancy correlated with loss of CHD7 occupancy. CHD7 physically interacts with Runx1 and suppresses Runx1-induced expansion of HSPCs during development, providing both physical and genetic evidence for the Runx1-CHD7 interaction. CHD7 modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
2023-01-01 | GSE130280 | GEO
Project description:Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. CHD7 chromatin immunoprecipitation in human CD34+ and mouse HSPCs revealed enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors, and decreased Runx1 occupancy correlated with loss of CHD7 occupancy. CHD7 physically interacts with Runx1 and suppresses Runx1-induced expansion of HSPCs during development, providing both physical and genetic evidence for the Runx1-CHD7 interaction. CHD7 modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
2023-01-01 | GSE84128 | GEO
Project description:Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. CHD7 chromatin immunoprecipitation in human CD34+ and mouse HSPCs revealed enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors, and decreased Runx1 occupancy correlated with loss of CHD7 occupancy. CHD7 physically interacts with Runx1 and suppresses Runx1-induced expansion of HSPCs during development, providing both physical and genetic evidence for the Runx1-CHD7 interaction. CHD7 modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
2023-01-01 | GSE84129 | GEO
Project description:miRNA-Sequencing of RUNX1 overexpressing K562 cells were compared to K562 cells transduced with an empty vector control to analyse the differential expression of miRNAs in hematopoiesis. K562 cells were transduced either with an empty lentiviral vector as control or a lentiviral vector overexpressing human RUNX1. The samples were biological triplicates and the results were validated by qRT-PCR using SYBR green.
2016-06-01 | E-GEOD-70942 | biostudies-arrayexpress
Project description:The transcription factor Runx1 is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cell (HSPC) pools. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. Here we describe a genome-scale RNAi screen to detect genes that cooperate with Runx1 in regulating HSPCs. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. We show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of HSPCs in vitro. We find an upregulation of HoxA cluster genes upon Pcgf1 knockdown that possibly accounts for the increase in self-renewal. Further, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1 together with the epigenetic repressor Pcgf1 is necessary for terminal differentiation. Thus, our work discovers a genetic link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation.
2012-06-18 | GSE33280 | GEO