Inhibition of SRC-mediated Integrin Signaling in Bone Marrow Niche Enhances Hematopoietic Stem Cell Function

Overview

Journal iScience

Publisher Cell Press

Date 2022 Oct 7

PMID 36204266

Authors

Irene Mariam Roy

P V Anu

Samantha Zaunz

Srinu Reddi

Aravind M Giri

Rithika Saroj Sankar

Sarah Schouteden

Joerg Huelsken

Catherine M Verfaillie

Satish Khurana

Affiliations

Soon will be listed here.

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 expression transcriptionally. Systemic deletion of Periostin, an Integrin-αv ligand, showed increased expression of in bone marrow (BM) niche. Pharmacological inhibition or CRISPR-Cas9-mediated deletion of SRC, resulted in a similar increase in the chemokine expression . 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 . This mechanism could be harnessed further to improve the hematopoietic function.

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