GEO DataSets

Analysis of fetal CD34+ HSPCs expressing N-terminal truncated GATA1-mutant (GATA1s) during myeloid differentiation for 4 and 14 days. GATA1s mutations are associated with transient leukemia (TL)- in Down syndrome neonates. Results provide insight into the role of GATA1s in TL pathogenesis.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 3 protocol, 3 time sets

Platform:

GPL6480

Series:

GSE56332

9 Samples

Download data: TXT

(Submitter supplied) Transient leukemia (TL) is evident in 5-10% of all neonates with Down syndrome (DS) and associated with N-terminal truncating GATA1-mutations (GATA1s). Here we analyzed the effect of on gene expression upon ectopic expression of Gata1s or Gata1, while simultaneously knocking down endogenous GATA1, in wild-type CD34+-hematopoietic stem and progenitor cells during myeloid differentiation. Ectopic expression of Gata1s, but not Gata1, in wild-type CD34+-hematopoietic stem and progenitor cells induced hyperproliferation of eosinophil promyelocytes in vitro. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS5368

Platform:

GPL6480

9 Samples

Download data: TXT

(Submitter supplied) Down syndrome AML is characterized by the presence of the pathgnonomic mutation in GATA1, which cooperates with other somatic mutations. In this study, we utilzed iPSCs derived from Down syndrome individuals bearing trisomy 21 and introduced disease-specific mutations using CRISPR-Cas9. Hematopoeitic stem and progenitor cells (HSPCs) obtained by hematopoeitic differentiation of these iPSCs, and megakaryocytes generated from the HSPCs (by culturing in megakaryocyte-specific media) were used for RNA sequencing analysis.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

18 Samples

Download data: TXT

(Submitter supplied) Patients with Down syndrome (DS, trisomy 21, T21) are at increased risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (ML-DS). Both TAM and ML-DS require prenatal somatic mutations in GATA1, resulting in the truncated isoform GATA1s. The mechanism by which individual chromosome 21 (HSA21) genes synergize with GATA1s for leukemic transformation is challenging to study, in part due to limited human cell models with wild type GATA1 or GATA1s. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

19 Samples

Download data: TSV

(Submitter supplied) The goal of this study is to define the global gene expression profile of primary leukemic blasts from patients with different forms of myeloid leukemia and different FAB subtypes. Here we report the global gene expression profile of 2 patients with AML FAB M5, 2 patients with AML FAB M7, 3 patients with Down syndrome AML FAB M7 and 3 patients with Down syndrome transient leukemia.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

10 Samples

Download data: CEL

(Submitter supplied) The goal of this study is to define miR-125b-2 target genes in the hematopoietic system by genetic alteration of miR-125b expression levels. Here we report the identification of miR-125b-2 targets in the hematopoietic system by repressing miR125b in megakaryoblastic leukemia (AMKL) cell lines and overexpressing miR-125b-2 in hematopoietic stem and progenitor cells (CD34+-HSPCs)

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

10 Samples

Download data: CEL

(Submitter supplied) Serial replated GFP + lineage negative cells from Gata1deltaneodeltaHS fetal liver hematopoietic progenitors for 4 generations in methocult M3234 under megakaryocyte promoting conditions, IL3, TPO, IL6, and IL11. Cells were subject to retro-viral infection with MIGR1GFP, MIGR1ETS2, MIGR1ERG, and MIGR1FLI1.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platform:

GPL6103

14 Samples

Download data

(Submitter supplied) We transduced mouse Gata1- megakaryocyte-erythroid progenitors with MIGRI-GFP vector expressing GATA1fl or GATA1s cDNAs. GFP-positive cells expressing one of the two isoforms of GATA1 were isolated by FACS 42 hours following transduction and used for microarray transcriptome analysis. At this time point, there was no apparent difference in the cell surface phenotypes between GATA1fl and GATA1s-expressing cells. more...

Organism:

Mus musculus

Type:

Expression profiling by array; Third-party reanalysis

Platform:

GPL1261

3 Samples

Download data: CEL, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below. Germline GATA1 mutations resulting in the production of an amino-truncated protein termed GATA1s (for “short”) cause congenital hypoplastic anemia. Similar somatic mutations promote transient myeloproliferative disease and acute megakaryoblastic leukemia in trisomy 21 patients. Here we show that induced pluripotent stem cells (iPSCs) from patients with GATA1-truncating mutations exhibit impaired erythroid potential but enhanced megakaryopoiesis and myelopoiesis, faithfully recapitulating the major phenotypes of associated diseases. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing; Third-party reanalysis

Platforms:

GPL1261 GPL6244 GPL13112

24 Samples

Download data: BROADPEAK, BW, CEL

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: BROADPEAK, BW

(Submitter supplied) We generated human induced pluripotent stem cells (iPSCs) from trisomy 21 (T21) and euploid patient tissues with and without GATA1 mutations causing exclusive expression of truncated GATA1, termed GATA1short (GATA1s). Transcriptome analysis comparing expression levels of genes in GATA1s vs. wtGATA1-expressing progenitors demonstrated that GATA1s impairs erythropoiesis and enhances megakaryopoiesis and myelopoiesis in both T21 and euploid contexts in the iPSC-model system.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

13 Samples

Download data: CEL

(Submitter supplied) Children with Down syndrome (DS) are at high risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (DS-AMKL). GATA1 gene mutations are detected in almost all TAM and DS-AMKL samples, leading to exclusive expression of short GATA1 protein (GATA1s) lacking of N-terminal domain (NTD). However, it remains to be clarified how GATA1s is involved with both disorders. To investigate how the loss of GATA1 NTD is involved in the molecular mechanisms of leukemogenesis in DS, we established the K562 GATA1s (K562-G1s) clones expressing only GATA1s by CRISPR/Cas9 genome editing. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing; Other

Platforms:

GPL21697 GPL15520

26 Samples

Download data: BED, BIGWIG, TXT

(Submitter supplied) Background: Children with Down syndrome (DS) are predisposed to acute megakaryoblastic leukemia (AMKL, or AML M7) and a related myeloid disorder, referred to as transient myeloproliferative disorder (TMD), or transient leukemia (TL). Recently, acquired mutations in the erythroid/megakaryocytic lineage-specific transcription factor GATA-1 have been identified in megakaryoblasts from virtually all DS patients with AMKL (DS-AMKL), as well as in nearly all DS neonates with TMD. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS1316

Platform:

GPL1261

10 Samples

Download data

Analysis of megakaryocytes and their progenitors from mutant E12.5 embryo liver expressing truncated transcription factor GATA-1. Results provide insight into the role of variant GATA-1 (GATA1s) in megakaryocyte hyperproliferation and Down syndrome (DS)-associated leukemias (TMD, DS-AMKL/DS-AML M7).

Organism:

Mus musculus

Type:

Expression profiling by array, count, 2 cell type, 3 genotype/variation sets

Platform:

GPL1261

Series:

GSE2433

10 Samples

Download data

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

6 Samples

Download data: CEL

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

4 Samples

Download data: CEL

(Submitter supplied) The goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis. To study this, we transduced an immortalized (but not transformed) cell line (derived from Gata1s mutant fetal liver progenitor through insertional mutagenesis) by Plag1-expressing retrovirus. This turned a non-transformed cell line to a leukemogenic cell line. To study whether Plag1 overexpression led to deregulation of signaling pathways that may contribute to leukemic transformation, we generated microarray gene expression profiles of this cell line transduced with either Plag1 or the empty vector.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

8 Samples

Download data: CEL

(Submitter supplied) The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

18 Samples

Download data: CEL

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

11 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platforms:

GPL1261 GPL570

47 Samples

Download data: CEL