Cited by 97Hematopoietic Stem Cell TransplantationAcute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processes

C/EBPα determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation

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Suh, Hyung Chan, Gooya, John, Renn, Katie, Friedman, Alan D., Johnson, Peter F., Keller, Jonathan R.·2006·Blood

Abstract

C/EBPα is an essential transcription factor required for myeloid differentiation. While C/EBPα can act as a cell fate switch to promote granulocyte differentiation in bipotential granulocyte-macrophage progenitors (GMPs), its role in regulating cell fate decisions in more primitive progenitors is not known. We found increased numbers of erythroid progenitors and erythroid cells in C/EBPα–/– fetal liver (FL). Also, enforced expression of C/EBPα in hematopoietic stem cells resulted in a loss of erythroid progenitors and an increase in myeloid cells by inhibition of erythroid development and inducing myeloid differentiation. Conditional expression of C/EBPα in murine erythroleukemia (MEL) cells induced myeloid-specific genes, while inhibiting erythroid-specific gene expression including erythropoietin receptor (EpoR), which suggests a novel mechanism to determine hematopoietic cell fate. Thus, C/EBPα functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors.

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  1. Perrotti D, Cesi V, Trotta R, et al. BCR-ABL sup- presses C/EBPalpha expression through inhibi- tory action of hnRNP E2. Nat Genet. 2002;30:48- 58.
  2. Ravet E, Reynaud D, Titeux M, et al. Character- ization of DNA-binding-dependent and -indepen- dent functions of SCL/TAL1 during human eryth- ropoiesis. Blood. 2004;103:3326-3335.

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Authors
Suh, H. C., Gooya, J., Renn, K., Friedman, A. D., Johnson, P. F., & Keller, J. R.
Affiliations
Johns Hopkins University (US)
Venue
Blood
Published
2006-06-01
Volume
107
Issue
11
Pages
4308-4316
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2048645509
Cited by
95
References
54
Citations by year
2026: 7 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 7 · 2014: 4 · 2013: 4 · 2012: 3
FWCI
3.85
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health (n01co12400-79-0-22, NO1-CO12400)
  • National Cancer Institute (N01CO12400, NO1‐CO‐12400)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Keywords
C/EBPα, erythroid differentiation, myeloid differentiation, hematopoietic stem cells, erythropoietin receptor, erythroid progenitor cells, CFU-GM, transcription factors, murine erythroleukemia cells, fetal liver
MeSH terms
Animals, Cell Count, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Hematopoiesis, Liver, Transfection, Receptors, Erythropoietin, Mice, Knockout, Myeloid Cells, CCAAT-Enhancer-Binding Protein-alpha, Multipotent Stem Cells, Erythroid Cells, Mice

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