Cited by 108Hematopoietic Stem Cell TransplantationCytokine Signaling Pathways and InteractionsMesenchymal stem cell research

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Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration

Chung, Yang-Jo, Park, Bo-Bae, Kang, Young-Ju, Kim, Tae-min, Eaves, Connie J., Oh, Il-Hoan·2006·Blood

DOI 10.1182/blood-2006-01-010199

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Abstract

Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting ability, but the signaling pathways that regulate this process remain poorly understood. Here we show that transduction of adult mouse bone marrow cells with a constitutively activated form of Stat3 (Stat3-C) increased their regenerative activity in lethally irradiated recipients. Conversely, transduction of these cells with a dominant-negative form of Stat3 suppressed their regenerative activity. Serial transplantation and clonal tracking of the HSC progeny regenerated in vivo from STAT3-C-transduced HSCs demonstrated that the major effect of forced expression of STAT3-C was to enhance HSC self-renewal during the initial phase of hematopoietic recovery. This acquired potential for enhanced self-renewal divisions then became latent, but was reactivated when the cells were transferred to new irradiated recipients. Increased levels of activated STAT3 were also found to be associated with greater preservation of primitive hematopoietic cells in short-term cultures. These results indicate a novel biphasic regulation of HSC self-renewal in vivo in which activated STAT3 promotes HSC self-renewal under stimulated, but not homeostatic, conditions. STAT3 may thus be an important regulator of hematopoietic regeneration and a novel target for HSC engineering.

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Authors: Chung, Y.-J., Park, B.-B., Kang, Y.-J., Kim, T.-M., Eaves, C. J., & Oh, I.-H.
Affiliations: BC Cancer Agency (CA)
ORCID: Kang, Young-Ju
Kim, Tae-min
Eaves, Connie J.
Oh, Il-Hoan
Venue: Blood
Publisher: American Society of Hematology
Published: 2006-08-15
Volume: 108
Issue: 4
Pages: 1208-1215
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2006-01-010199
OpenAlex: W2166180289
Semantic Scholar: 5d35bdca0b6f9dfa9fac5e3966d0a3779f0ec0a0
Cited by: 107
References: 40
Citations by year: 2025: 4 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 9 · 2012: 4
FWCI: 5.01
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: STAT3, hematopoietic stem cells, self-renewal, hematopoietic regeneration, STAT3 activation, dominant-negative STAT3, bone marrow transplantation, irradiation, clonal tracking, serial transplantation
MeSH terms: Animals, Cell Division, Cells, Cultured, Enzyme Activation, Gene Expression Regulation, Hematopoietic Stem Cells, Mice, Transgenic, Regeneration, Transduction, Genetic, Whole-Body Irradiation, Signal Transduction, Bone Marrow Transplantation, STAT3 Transcription Factor, Mice

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Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration

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