Inhibition of SRC-mediated integrin signaling in bone marrow niche enhances hematopoietic stem cell function.

Autor:	Roy IM; School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India., Anu PV; School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India., Zaunz S; Stem Cell Institute, KU Leuven, 3000 Leuven, Belgium., Reddi S; School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India., Giri AM; School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India., Sankar RS; School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India., Schouteden S; Stem Cell Institute, KU Leuven, 3000 Leuven, Belgium., Huelsken J; École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Verfaillie CM; Stem Cell Institute, KU Leuven, 3000 Leuven, Belgium., Khurana S; School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Sep 19; Vol. 25 (10), pp. 105171. Date of Electronic Publication: 2022 Sep 19 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.105171
Abstrakt:	Interaction with microenvironmental factors is crucial for the regulation of hematopoietic stem cell (HSC) function. Stroma derived factor (SDF)-1α supports HSCs in the quiescent state and is central to the homing of transplanted HSCs. Here, we show that integrin signaling regulates Sdf-1α expression transcriptionally. Systemic deletion of Periostin, an Integrin-αv ligand, showed increased expression of Sdf-1α in bone marrow (BM) niche. Pharmacological inhibition or CRISPR-Cas9-mediated deletion of SRC, resulted in a similar increase in the chemokine expression in vitro . Importantly, systemic SRC-inhibition led to increase in SDF-1α levels in BM plasma. This resulted in a robust increase (14.05 ± 1.22% to 29.11 ± 0.69%) in the homing efficiency of transplanted HSCs. In addition, we observed enhancement in the recovery of blood cell counts following radiation injury, indicating an enhanced hematopoietic function. These results establish a role of SRC-mediated integrin signaling in the transcriptional regulation of Sdf-1α . This mechanism could be harnessed further to improve the hematopoietic function. Competing Interests: The authors declare no competing interests. (© 2022 The Authors.)
Databáze:	MEDLINE
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