Tgfb1 deficiency impairs the self-renewal capacity of murine hematopoietic stem/progenitor cells in vivo
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
Transforming growth factor β1 (TGFB1) refers to a pleiotropic cytokine exerting contrasting roles in hematopoietic stem cells (HSCs) functions in vitro and in vivo. However, the understanding of hematopoiesis in vivo, when TGFB1 is constantly deactivated, is still unclear, mainly due to significant embryonic lethality and the emergence of a fatal inflammatory condition, which makes doing these investigations challenging. Our study aims to find the specific role of TGFB1 in regulating hematopoiesis in vivo. We engineered mice strains (Vav1 or Mx1 promoter-driven TGFB1 knockout) with conditional knockout of TGFB1 to study its role in hematopoiesis in vivo. In fetal and adult hematopoiesis, TGFB1 KO mice displayed deficiency and decreased self-renewal capacity of HSCs with myeloid-biased differentiation. The results were different from the regulating role of TGFB1 in vitro. Additionally, our results showed that TGFB1 deficiency from fetal hematopoiesis stage caused more severe defect of HSCs than in the adult stage. Mechanistically, our findings identified TGFB1-SOX9-FOS/JUNB/TWIST1 signal axis as an essential regulating pathway in HSCs homeostasis. Our study may provide a scientific basis for clinical HSC transplantation and expansion.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:703 |
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| Enthalten in: |
Biochemical and biophysical research communications - 703(2024) vom: 09. März, Seite 149686 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yizhou [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 13.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2024.149686 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Transforming growth factor β1 (TGFB1) refers to a pleiotropic cytokine exerting contrasting roles in hematopoietic stem cells (HSCs) functions in vitro and in vivo. However, the understanding of hematopoiesis in vivo, when TGFB1 is constantly deactivated, is still unclear, mainly due to significant embryonic lethality and the emergence of a fatal inflammatory condition, which makes doing these investigations challenging. Our study aims to find the specific role of TGFB1 in regulating hematopoiesis in vivo. We engineered mice strains (Vav1 or Mx1 promoter-driven TGFB1 knockout) with conditional knockout of TGFB1 to study its role in hematopoiesis in vivo. In fetal and adult hematopoiesis, TGFB1 KO mice displayed deficiency and decreased self-renewal capacity of HSCs with myeloid-biased differentiation. The results were different from the regulating role of TGFB1 in vitro. Additionally, our results showed that TGFB1 deficiency from fetal hematopoiesis stage caused more severe defect of HSCs than in the adult stage. Mechanistically, our findings identified TGFB1-SOX9-FOS/JUNB/TWIST1 signal axis as an essential regulating pathway in HSCs homeostasis. Our study may provide a scientific basis for clinical HSC transplantation and expansion | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hematopoiesis | |
| 650 | 4 | |a Hematopoietic stem/progenitor cells (HSPCs) | |
| 650 | 4 | |a In vivo | |
| 650 | 4 | |a Myeloid-biased differentiation | |
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| 650 | 4 | |a Tgfb1 | |
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| 700 | 1 | |a Xu, Zihan |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Lingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shengnan |e verfasserin |4 aut | |
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