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

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

  • iScience. 2022 Sep 19;25(10):105171. doi: 10.1016/j.isci.2022.105171.
Irene Mariam Roy 1,  P V Anu 1,  Samantha Zaunz 2,  Srinu Reddi 1,  Aravind M Giri 1,  Rithika Saroj Sankar 1,  Sarah Schouteden 2,  Joerg Huelsken 3,  Catherine M Verfaillie 2,  Satish Khurana 1
Affiliations

Affiliations

  • 1 School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Kerala 695551, India.
  • 2 Stem Cell Institute, KU Leuven, 3000 Leuven, Belgium.
  • 3 École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
PMID: 36204266 DOI: 10.1016/j.isci.2022.105171
Abstract

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.

Keywords

Biological sciences; cell biology; stem cells research.

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