Cited by 541Hematopoietic Stem Cell TransplantationHemoglobinopathies and Related DisordersGenomics and Chromatin Dynamics

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Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells.

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Weiss, M J, Keller, G, Orkin, S H·1994·Genes & Development

DOI 10.1101/gad.8.10.1184

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Abstract

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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Authors: Weiss, M. J., Keller, G., & Orkin, S. H.
Affiliations: Dana-Farber Cancer Institute (US)
ORCID: Weiss, M J
Keller, G
Orkin, S H
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
DOI: 10.1101/gad.8.10.1184
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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Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells.

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