SOCS3 Is Essential in the Regulation of Fetal Liver Erythropoiesis
Open accessAbstract
SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene-mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an embryonic lethality at 12-16 days associated with marked erythrocytosis. Moreover, the in vitro proliferative capacity of progenitors is greatly increased. SOCS3-deficient fetal liver stem cells can reconstitute hematopoiesis in lethally irradiated adults, indicating that its absence does not disturb bone marrow erythropoiesis. Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis.
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Constitutive expression or ablation of SOCS-3 results in embryonic death.
“These expression systems require conditional expression of SOCS-3 within the parenchymal cells of the liver since constitutive expression or ablation results in embryonic death (40).”
From Expression of suppressors of cytokine signaling during liver regeneration (2001) · cites this paper as [40]
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- Authors
- Marine, J.-C., McKay, C., Wang, D., Topham, D. J., Parganas, E., Nakajima, H., Pendeville, H., Yasukawa, H., Sasaki, A., Yoshimura, A., & Ihle, J. N.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Kurume University (JP)
- Corresponding author
- Ihle, James N
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 98
- Issue
- 5
- Pages
- 617-627
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2033881557
- Cited by
- 372
- References
- 3
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 12 · 2013: 9 · 2012: 16
- FWCI
- 14.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
- Funders
- American Lebanese Syrian Associated Charities (CA 21765)
- National Heart, Lung, and Blood Institute (P01HL053749, P01HL53749)
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK42932, R01DK042932)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- SOCS3, erythropoiesis, embryonic lethality, erythrocytosis, erythroid progenitor proliferation, fetal liver hematopoiesis, JAK3, cytokine signaling inhibition, hematopoietic stem cells, transgenic overexpression
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, Dose-Response Relationship, Drug, Erythropoiesis, Flow Cytometry, Hematopoiesis, Interleukin-2, Liver, Mice, Mutant Strains, Models, Genetic, Phenotype, Proteins, Repressor Proteins, Time Factors, Transcription Factors, Transfection, Interleukin-4, Mutagenesis, In Situ Hybridization, Gene Expression Regulation, Developmental, Suppressor of Cytokine Signaling Proteins, Mice
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