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Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells.
Open accessAbstract
Mouse embryonic stem (ES) cells lacking the transcription factor GATA-1 do not produce mature red blood cells either in vivo or in vitro. To define the consequences of GATA-1 loss more precisely, we used an in vitro ES cell differentiation assay that permits enumeration of primitive (EryP) and definitive (EryD) erythroid precursors and recovery of pure erythroid colonies. In contrast to normal ES cells, GATA-1- ES cells fail to generate EryP precursors. EryD precursors, however, are normal in number but undergo developmental arrest and death at the proerythroblast stage. Contrary to initial expectations, arrested GATA-1(-)-definitive proerythroblasts express GATA target genes at normal levels. Transcripts of the related factor GATA-2 are remarkably elevated in GATA-1- proerythroblasts. These findings imply substantial interchangeability of GATA factors in vivo and suggest that GATA-1 normally serves to repress GATA-2 during erythropoiesis. The approach used here is a paradigm for the phenotypic analysis of targeted mutations affecting hematopoietic development.
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“Some of these perturbations are known to be indispensable for their corresponding cell type, including GATA1 for erythroid cells such as K56221 and HMGCR for T-cells such as Jurkat22, but most had no previously documented explanation for their cell-type dependent effects.”
From Transcriptome-wide analysis of differential expression in perturbation atlases (2025) · cites this paper as [21]
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Metadata
- Authors
- Weiss, M. J., Keller, G., & Orkin, S. H.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1994-05-15
- Volume
- 8
- Issue
- 10
- Pages
- 1184-1197
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2147951044
- Cited by
- 541
- References
- 84
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 1 · 2014: 6 · 2013: 14 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Amgen
- National Institutes of Health (5r01dk043285-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-43285)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- erythroid development, GATA-1, GATA2, embryonic stem cells, erythropoiesis, erythroid precursors, proerythroblasts, transcriptional repression, hematopoietic development, targeted mutations
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Line, DNA-Binding Proteins, Erythroblasts, Erythropoiesis, Globins, Hematopoietic Stem Cells, Molecular Sequence Data, Proto-Oncogene Proteins, RNA, Messenger, Transcription Factors, Trans-Activators, Erythroid Precursor Cells, Up-Regulation, Cell Death, Gene Expression Regulation, Developmental, Proto-Oncogene Proteins c-myb, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, GATA2 Transcription Factor, GATA3 Transcription Factor, Mice
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