Expression data from Fog1+/+ and Fog1 ki/ki mouse megakaryocyte-erythroid progenitors (MEP).
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19497 | GEO | 2010/04/11
SECONDARY ACCESSION(S): PRJNA122415
REPOSITORIES: GEO
Similar Datasets
Project description:The transcription co-factor FOG1 interacts with the chromatin remodeling complex NuRD to mediate gene activation and gene repression during hematopoiesis. We have generated mice with a targeted mutation in the endogenous Fog1 locus that results in an N-ternimal mutation in FOG1 that disrupts the interaction with NuRD. We used gene expression microarrays to explore the global transcriptional programs regulated by FOG1 and NuRD in megakaryocyte-erythroid progenitors (MEP) to aid in understanding its role during hematopoiesis. Flow cytometry was used to isolate Megakaryocyte-Erythroid progenitors (MEP) from murine bone marrow. MEP were identified as Lineage neg, kit pos, Sca1 neg, CD34 neg, FcgrII/III low cells.
2010-04-11 | E-GEOD-19497 | biostudies-arrayexpress
Project description:The transcription co-factor FOG1 interacts with the chromatin remodeling complex NuRD to mediate gene activation and gene repression during hematopoiesis. We have generated mice with a targeted mutation in the endogenous Fog1 locus that results in an N-ternimal mutation in FOG1 that disrupts the interaction with NuRD. We used gene expression microarrays to explore the global transcriptional programs regulated by FOG1 and NuRD in megakaryocytic cells to aid in understanding its role during hematopoiesis.
2011-06-28 | GSE29975 | GEO
Project description:The transcription co-factor FOG1 interacts with the chromatin remodeling complex NuRD to mediate gene activation and gene repression during hematopoiesis. We have generated mice with a targeted mutation in the endogenous Fog1 locus that results in an N-ternimal mutation in FOG1 that disrupts the interaction with NuRD. We used gene expression microarrays to explore the global transcriptional programs regulated by FOG1 and NuRD in megakaryocytic cells to aid in understanding its role during hematopoiesis. Bovine serum albumin (BSA) gradient centrifugation was used to isolate maturated megakaryocutes from mouse
2011-06-28 | E-GEOD-29975 | biostudies-arrayexpress
Project description:Background: Recent advances in single-cell techniques have provided the opportunity to finely dissect cellular heterogeneity within populations previously defined by “bulk” assays and to uncover rare cell types. In human hematopoiesis, megakaryocytes and erythroid cells differentiate from a shared precursor, the megakaryocyte-erythroid progenitor (MEP), which remains poorly defined.Results: To clarify the cellular pathway in erythro-megakaryocyte differentiation, we correlated the surface immunophenotype, transcriptional profile and differentiation potential of individual MEP cells. Highly purified, single MEP cells (n=681) were analyzed using index fluorescence-activated cell sorting with parallel targeted transcriptional profiling of the same cells performed using a specifically designed panel of 87 genes. Differentiation potential was tested in novel, single-cell differentiation assays. Our results demonstrated that immunophenotypic MEP in fact comprise three distinct subpopulations: (1) “Pre-MEP”, enriched for erythroid/megakaryocyte progenitors but with residual myeloid differentiation capacity (2) “E-MEP”, strongly biased towards erythroid differentiation, and (3) “MK-MEP”, a previously undescribed, rare population of cells that are bipotent but primarily generate megakaryocytic progeny. Therefore, conventionally-defined MEP are in fact a mixed population: a minority give rise to mixed-lineage colonies while the majority of cells are transcriptionally-primed to generate exclusively single-lineage output. Conclusions: Our study clarifies the cellular hierarchy in human megakaryocyte/erythroid lineage commitment and highlights the importance of using a combination of single-cell approaches to dissect cellular heterogeneity and identify rare cell types within a population. We present a novel immunophenotyping strategy that enables the prospective identification of specific intermediate progenitor populations in erythro-megakaryopoiesis, allowing for in-depth study of disorders including inherited cytopenias, myeloproliferative disorders and erythromegakaryocytic leukemias.
2016-04-02 | GSE79331 | GEO
Project description:This collection contains microRNA expression profiling data for samples purified from umbilical cord blood, belonging to one of the followiing populations: MEP, MEGA1, MEGA2, ERY1, ERY2, ERY3. MEP: megakaryocyte-erythrocyte precursors (defined by CD34+ CD38+ IL-3Ra- CD45RA- ); MEGA1: megakaryocyte population 1 (defined by CD34+ CD61+ CD41+ CD45- ); MEGA2: megakaryocyte population 2 (defined by CD34- CD61+ CD41+ CD45- ); ERY1: erythrocyte population 1 (defined by CD34+ CD71+ GlyA- ); ERY2: erythrocyte population 2 (defined by CD34- CD71+ GlyA- ); ERY3: erythrocyte population 3 (defined by CD34- CD71+ GlyA+ ). Keywords: microRNA, miRNA, MEP, megakaryocyte, erythrocyte, lineage specification
2008-06-10 | GSE10593 | GEO
Project description:Background: Recent advances in single-cell techniques have provided the opportunity to finely dissect cellular heterogeneity within populations previously defined by âbulkâ assays and to uncover rare cell types. In human hematopoiesis, megakaryocytes and erythroid cells differentiate from a shared precursor, the megakaryocyte-erythroid progenitor (MEP), which remains poorly defined.Results: To clarify the cellular pathway in erythro-megakaryocyte differentiation, we correlated the surface immunophenotype, transcriptional profile and differentiation potential of individual MEP cells. Highly purified, single MEP cells (n=681) were analyzed using index fluorescence-activated cell sorting with parallel targeted transcriptional profiling of the same cells performed using a specifically designed panel of 87 genes. Differentiation potential was tested in novel, single-cell differentiation assays. Our results demonstrated that immunophenotypic MEP in fact comprise three distinct subpopulations: (1) âPre-MEPâ, enriched for erythroid/megakaryocyte progenitors but with residual myeloid differentiation capacity (2) âE-MEPâ, strongly biased towards erythroid differentiation, and (3) âMK-MEPâ, a previously undescribed, rare population of cells that are bipotent but primarily generate megakaryocytic progeny. Therefore, conventionally-defined MEP are in fact a mixed population: a minority give rise to mixed-lineage colonies while the majority of cells are transcriptionally-primed to generate exclusively single-lineage output. Conclusions: Our study clarifies the cellular hierarchy in human megakaryocyte/erythroid lineage commitment and highlights the importance of using a combination of single-cell approaches to dissect cellular heterogeneity and identify rare cell types within a population. We present a novel immunophenotyping strategy that enables the prospective identification of specific intermediate progenitor populations in erythro-megakaryopoiesis, allowing for in-depth study of disorders including inherited cytopenias, myeloproliferative disorders and erythromegakaryocytic leukemias. Multiplex RT-PCR gene expression profiling of 807 human megakaryocyte-erythroid progenitor cells (MEP) isolated from three healthy donors by apheresis following G-CSF treatment. Cells were excluded if more than 70 assays did not result in amplification or displayed Ct higer than 13 for B2M or higher than 15 for GAPDH. Furthermore cells with a mean non-dropout Ct value greater than 20 were removed. This resulted in a dataset of 681 cells, which were subsequently normalised to the mean of B2M and GAPDH expression.
2016-04-02 | E-GEOD-79331 | biostudies-arrayexpress
Project description:This collection contains microRNA expression profiling data for samples purified from umbilical cord blood, belonging to one of the followiing populations: MEP, MEGA1, MEGA2, ERY1, ERY2, ERY3. MEP: megakaryocyte-erythrocyte precursors (defined by CD34+ CD38+ IL-3Ra- CD45RA- ); MEGA1: megakaryocyte population 1 (defined by CD34+ CD61+ CD41+ CD45- ); MEGA2: megakaryocyte population 2 (defined by CD34- CD61+ CD41+ CD45- ); ERY1: erythrocyte population 1 (defined by CD34+ CD71+ GlyA- ); ERY2: erythrocyte population 2 (defined by CD34- CD71+ GlyA- ); ERY3: erythrocyte population 3 (defined by CD34- CD71+ GlyA+ ). Keywords: microRNA, miRNA, MEP, megakaryocyte, erythrocyte, lineage specification Varied numbers of samples were analyzed per population. Each sample came from one donor. Data were normalized as described (Lu et al., Nature 435, 834-838, 2005) with modifications. Average readings from water-only labeled samples were used for probe-specific background subtraction. Linear normalization among different bead sets for the same sample was performed using readings from 2 post-control probes with equal contribution. Sample normalization was subsequently carried out assuming equal total fluorescence readings.
2010-06-26 | E-GEOD-10593 | biostudies-arrayexpress
Project description:Expression data from Fog1+/+ and Fog1 ki/ki mouse megakaryocyte-erythroid progenitors (MEP).
| PRJNA122415 | ENA
Project description:The differentiation of primary human megakaryocyte-erythroid progenitors (MEP) into megakaryocytic (Mk) or erythroid (E) progenitors is critical for maintaining the blood system, yet the mechanisms that regulate this fate specification remain unclear. Here, we analyzed RNA-seq data and found that RUNX1 is a key regulator of differential gene expression in MEP fate specification. Through viral transduction of primary MEP with RUNX1, we demonstrated that overexpression of RUNX1 promotes Mk over E specification, whereas pan-RUNX inhibition promotes E fate specification over Mk. We found that although the levels of total RUNX1 do not differ between MkP and ErP, MkP have higher levels of RUNX1 phosphorylated serine residues, and that serine/threonine phosphorylation of RUNX1 dramatically increases its effectiveness. We used human erythroleukemia (HEL) cell lines with expression of HA-tagged WT RUNX1, phosphomimetic (RUNX1-4D) and non-phosphorylatable (RUNX1-4A) mutants to model their effects on MEP. Although the chromatin association was not informative, the three forms of RUNX1 caused differential expression of 2,625 genes. Approximately 40% of these differentially expressed genes (DEGs) showed an increase with both RUNX1-WT and RUNX1-4D while another 40% showed a decrease with both RUNX1-WT and RUNX1-4D. We compared these DEGs with DEGs from primary human MEP, Mk progenitors (MkP), and E progenitors (ErP), and found that the genes upregulated by WT and RUNX1-4D in HEL cells overlapped significantly with the genes upregulated in MkP vs. MEP, whereas genes downregulated by WT and RUNX1-4D in HEL cells overlapped significantly with the genes downregulated in MkP vs. MEP. These results suggest that phosphorylation of RUNX1 enhances RUNX1’s function to activate or repress transcription of target genes that are up/downregulated during MEP fate specification.
2024-09-24 | GSE232877 | GEO
Project description:The differentiation of primary human megakaryocyte-erythroid progenitors (MEP) into megakaryocytic (Mk) or erythroid (E) progenitors is critical for maintaining the blood system, yet the mechanisms that regulate this fate specification remain unclear. Here, we analyzed RNA-seq data and found that RUNX1 is a key regulator of differential gene expression in MEP fate specification. Through viral transduction of primary MEP with RUNX1, we demonstrated that overexpression of RUNX1 promotes Mk over E specification, whereas pan-RUNX inhibition promotes E fate specification over Mk. We found that although the levels of total RUNX1 do not differ between MkP and ErP, MkP have higher levels of RUNX1 phosphorylated serine residues, and that serine/threonine phosphorylation of RUNX1 dramatically increases its effectiveness. We used human erythroleukemia (HEL) cell lines with expression of HA-tagged WT RUNX1, phosphomimetic (RUNX1-4D) and non-phosphorylatable (RUNX1-4A) mutants to model their effects on MEP. Although the chromatin association was not informative, the three forms of RUNX1 caused differential expression of 2,625 genes. Approximately 40% of these differentially expressed genes (DEGs) showed an increase with both RUNX1-WT and RUNX1-4D while another 40% showed a decrease with both RUNX1-WT and RUNX1-4D. We compared these DEGs with DEGs from primary human MEP, Mk progenitors (MkP), and E progenitors (ErP), and found that the genes upregulated by WT and RUNX1-4D in HEL cells overlapped significantly with the genes upregulated in MkP vs. MEP, whereas genes downregulated by WT and RUNX1-4D in HEL cells overlapped significantly with the genes downregulated in MkP vs. MEP. These results suggest that phosphorylation of RUNX1 enhances RUNX1’s function to activate or repress transcription of target genes that are up/downregulated during MEP fate specification.
2024-09-24 | GSE232879 | GEO