Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA122711 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE16676: Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1 GSE16677: Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples GSE16679: Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia GSE16682: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors GSE16684: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling Refer to individual Series
2010-08-01 | E-GEOD-16655 | biostudies-arrayexpress
Project description:In this project, we studied a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the GATA1 transcription factor (called GATA1s mutation). The model was generated through retroviral insertional mutagenesis in Gata1s mutant fetal liver progenitors. In this study, we analyzed the dependency of these leukemic cells on the Gata1s mutant protein. Here we report Gata1s mutant leukemic cells were dependent on this mutant protein. Introduction of the full-length Gata1 protein to these cells led to their reduced proliferation and increased differentiation along the megakaryocytic lineage. We transduced leukemic cells with Gata1/estrogen receptor fusion cDNA (Gata1-ER) and generated stable cell lines. Addition of beta-estradiol to culture medium led to activation of the full-length Gata1 protein in synchronized leukemic cells. Gene expression profiles were collected at multiple time points.
2010-08-01 | E-GEOD-16676 | biostudies-arrayexpress
Project description:In this project, we studied a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the GATA1 transcription factor (called GATA1s mutation). The model was generated through retroviral insertional mutagenesis in Gata1s mutant fetal liver progenitors. In this study, we analyzed the dependency of these leukemic cells on the Gata1s mutant protein. Here we report Gata1s mutant leukemic cells were dependent on this mutant protein. Introduction of the full-length Gata1 protein to these cells led to their reduced proliferation and increased differentiation along the megakaryocytic lineage.
2010-08-01 | GSE16676 | GEO
Project description:The goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation. Here we report one such cell line [T6(6)] that gives rise to megakaryocytic leukemia (M7 leukemia) upon transplantation. Since the leukemic cells were retrovirally tagged with a GFP reporter, we sorted GFP+ leukemic blasts and generated their expression profiles by microarray.
2010-08-01 | E-GEOD-16682 | biostudies-arrayexpress
Project description:The goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation. Here we report one such cell line [T6(6)] that gives rise to megakaryocytic leukemia (M7 leukemia) upon transplantation.
2010-08-01 | GSE16682 | GEO
Project description:We used chromatin immunoprecipitation sequencing (ChIP-seq) to compare genome-wide binding profiles of GATA1fl and GATA1s in G1ME cells, which are immortalized, developmentally arrested megakaryocyte-erythroid progenitors (MEPs) derived from in vitro differentiation of murine Gata1- ES cells. Although the truncation in GATA1s leaves the DNA binding domain intact, GATA1s fails to broadly occupy erythroid specific regulatory regions. These observations point to lineage specific co-factor associations essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. We performed ChIP-seq on G1ME cells 42 hours after retroviral transfer of HA-tagged full-length GATA1 (GATA1fl) or GATA1s cDNAs (2 replicates each). At this time point, there was no apparent difference in the cell surface phenotypes between GATA1fl and GATA1s-expressing cells. For each ChIP-seq replicate we obtained a matching input sample (non-ChIP DNA) as a control.
2015-01-26 | E-GEOD-61932 | biostudies-arrayexpress
Project description:The goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation. Here we report one such cell line [T6(6)] that gives rise to megakaryocytic leukemia (M7 leukemia) upon transplantation. We show knockdown of IGF1R in these cells leads to their reduced proliferation.
2010-08-01 | GSE16684 | GEO
Project description:Mutations in GATA1 that result in skipping of exon 2, which encodes the N-terminus, are associated with the myeloid leukemia of Down syndrome and Diamond-Blackfan anemia (DBA). To elucidate the molecular functions of the N-terminus, we employed single-cell RNA sequencing (scRNA-seq) of fetal liver cells derived from Gata1 mutant embryos that express the GATA1 short (GATA1s) isoform in place of full-length GATA1 (GATA1FL). scRNA-seq highlighted defects in erythropoiesis and revealed that the absence of the N-terminus resulted in elevated expression of genes involved in glycolysis, such as the rate-limiting pyruvate kinase PKM. To elucidate the regulation of the PKM gene, we performed precision nuclear run-on sequencing and cleavage under targets and release using nuclease on erythroid cells following acute deletion of GATA1 and determined that PKM is a direct target of GATA1. Mechanistically, we found that substitution of GATA1FL with GATA1s led to increased glycolysis in erythroid progenitor cells but did not affect oxidative phosphorylation. We further discovered that the expression of PKM is significantly elevated in DBA patients with RPS19 mutations, consistent with a role for GATA1 regulation of glycolysis in erythropoiesis. Together, these findings reveal that GATA1 controls not just heme metabolism, but also glycolysis.
2026-01-12 | GSE316151 | GEO
Project description:Mutations in GATA1 that result in skipping of exon 2, which encodes the N-terminus, are associated with the myeloid leukemia of Down syndrome and Diamond-Blackfan anemia (DBA). To elucidate the molecular functions of the N-terminus, we employed single-cell RNA sequencing (scRNA-seq) of fetal liver cells derived from Gata1 mutant embryos that express the GATA1 short (GATA1s) isoform in place of full-length GATA1 (GATA1FL). scRNA-seq highlighted defects in erythropoiesis and revealed that the absence of the N-terminus resulted in elevated expression of genes involved in glycolysis, such as the rate-limiting pyruvate kinase PKM. To elucidate the regulation of the PKM gene, we performed precision nuclear run-on sequencing and cleavage under targets and release using nuclease on erythroid cells following acute deletion of GATA1 and determined that PKM is a direct target of GATA1. Mechanistically, we found that substitution of GATA1FL with GATA1s led to increased glycolysis in erythroid progenitor cells but did not affect oxidative phosphorylation. We further discovered that the expression of PKM is significantly elevated in DBA patients with RPS19 mutations, consistent with a role for GATA1 regulation of glycolysis in erythropoiesis. Together, these findings reveal that GATA1 controls not just heme metabolism, but also glycolysis.
2026-01-12 | GSE315985 | GEO
Project description:Mutations in GATA1 that result in skipping of exon 2, which encodes the N-terminus, are associated with the myeloid leukemia of Down syndrome and Diamond-Blackfan anemia (DBA). To elucidate the molecular functions of the N-terminus, we employed single-cell RNA sequencing (scRNA-seq) of fetal liver cells derived from Gata1 mutant embryos that express the GATA1 short (GATA1s) isoform in place of full-length GATA1 (GATA1FL). scRNA-seq highlighted defects in erythropoiesis and revealed that the absence of the N-terminus resulted in elevated expression of genes involved in glycolysis, such as the rate-limiting pyruvate kinase PKM. To elucidate the regulation of the PKM gene, we performed precision nuclear run-on sequencing and cleavage under targets and release using nuclease on erythroid cells following acute deletion of GATA1 and determined that PKM is a direct target of GATA1. Mechanistically, we found that substitution of GATA1FL with GATA1s led to increased glycolysis in erythroid progenitor cells but did not affect oxidative phosphorylation. We further discovered that the expression of PKM is significantly elevated in DBA patients with RPS19 mutations, consistent with a role for GATA1 regulation of glycolysis in erythropoiesis. Together, these findings reveal that GATA1 controls not just heme metabolism, but also glycolysis.
2026-01-12 | GSE315981 | GEO