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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 26, 2015 |
| Title |
Pluripotent stem cells reveal novel erythroid activities of the GATA1 N-terminus |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
Third-party reanalysis
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| Summary |
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. Similarly, GATA1s promotes megakaryopoiesis but not erythropoiesis in developmentally arrested Gata1- murine megakaryocyte-erythroid progenitors derived from murine embryonic stem cells (ESCs). Transcriptome studies demonstrate a selective deficiency in the ability of GATA1s to activate erythroid-expressed genes within populations of hematopoietic progenitors. Although its DNA binding domain is intact, chromatin immunoprecipitation studies show that GATA1s binding at specific erythroid regulatory regions is impaired, while binding at many non-erythroid sites, including megakaryocytic and myeloid target genes, is normal. These observations point to lineage specific GATA1 co-factor associations essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. More broadly, our studies underscore the value of ESCs and iPSCs to recapitulate and study disease phenotypes.
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| Overall design |
Refer to individual Series
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| Citation(s) |
25621499 |
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| Submission date |
Sep 30, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ross Hardison |
| E-mail(s) |
rch8@psu.edu
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| Organization name |
Pennsylvania State University
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| Street address |
303 Wartik Lab
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| City |
University Park |
| State/province |
PA |
| ZIP/Postal code |
16802 |
| Country |
USA |
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| Platforms (3) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (24)
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| GSM901041 |
CD43+/41+/235+ progenitors generated from T21/wtGATA1 iPSC line, biological rep1 |
| GSM901042 |
CD43+/41+/235+ progenitors generated from T21/wtGATA1 iPSC line, biological rep2 |
| GSM901043 |
CD43+/41+/235+ progenitors generated from T21/wtGATA1 iPSC line, biological rep3 |
| GSM901044 |
CD43+/41+/235+ progenitors generated from T21/wtGATA1 iPSC line, biological rep4 |
| GSM901045 |
CD43+/41+/235+ progenitors generated from T21/wtGATA1 iPSC line, biological rep5 |
| GSM901046 |
CD43+/41+/235+ progenitors generated from T21/wtGATA1 iPSC line, biological rep6 |
| GSM901047 |
CD43+/41+/235+ progenitors generated from T21/GATA1s iPSC line, biological rep1 |
| GSM901048 |
CD43+/41+/235+ progenitors generated from T21/GATA1s iPSC line, biological rep2 |
| GSM901049 |
CD43+/41+/235+ progenitors generated from T21/GATA1s iPSC line, biological rep3 |
| GSM1517424 |
CD43+/41+/235+ progenitors generated from euploid/wtGATA1 iPSC line, biological rep1 |
| GSM1517425 |
CD43+/41+/235+ progenitors generated from euploid/wtGATA1 iPSC line, biological rep2 |
| GSM1517426 |
CD43+/41+/235+ progenitors generated from euploid/GATA1s iPSC line, biological rep1 |
| GSM1517427 |
CD43+/41+/235+ progenitors generated from euploid/GATA1s iPSC line, biological rep2 |
| GSM1517428 |
GATA1fl_rep1 |
| GSM1517429 |
GATA1fl_rep2 |
| GSM1517430 |
GATA1s_rep1 |
| GSM1517431 |
GATA1s_rep2 |
| GSM1517432 |
input_GATA1fl_rep1 |
| GSM1517433 |
input_GATA1fl_rep2 |
| GSM1517434 |
input_GATA1s_rep1 |
| GSM1517435 |
input_GATA1s_rep2 |
| GSM1535475 |
G1ME_GATA1s_rep1 |
| GSM1535476 |
G1ME_GATA1s_rep2 |
| GSM1535477 |
G1ME_GATA1s_rep3 |
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| This SuperSeries is composed of the following SubSeries: |
| GSE36787 |
Transcriptome profiling of trisomy 21 and euploid iPSC-derived hematopoietic progenitors expressing wtGATA1 or an amino-truncated isoform of GATA1, GATA1short (GATA1s). |
| GSE61932 |
Genome-wide binding analysis of GATA1fl and GATA1s in G1ME cells. |
| GSE62879 |
Transcriptome profiling of mouse Gata1- megakaryocyte-erythroid progenitors (G1MEs) expressing one of the two isoforms of GATA1: full-length (GATA1fl) or an amino-truncated form of GATA1 (GATA1s). |
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| Relations |
| BioProject |
PRJNA262697 |
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