Niche-Mediated Integrin Signaling Supports Steady-State Hematopoiesis in the Spleen

Abstract

Outside-in integrin signaling regulates cell fate decisions in a variety of cell types, including hematopoietic stem cells (HSCs). Our earlier published studies showed that interruption of periostin (POSTN) and integrin-αv (ITGAV) interaction induces faster proliferation in HSCs with developmental stage–dependent functional effects. In this study, we examined the role of POSTN–ITGAV axis in lymphohematopoietic activity in spleen that hosts a rare population of HSCs, the functional regulation of which is not clearly known. Vav-iCre–mediated deletion of Itgav in the hematopoietic system led to higher proliferation rates, resulting in increased frequency of primitive HSCs in the adult spleen. However, in vitro CFU-C assays demonstrated a poorer differentiation potential following Itgav deletion. This also led to a decrease in the white pulp area with a significant decline in the B cell numbers. Systemic deletion of its ligand, POSTN, phenocopied the effects noted in Vav-Itgav−/− mice. Histological examination of Postn-deficient spleen also showed an increase in the spleen trabecular areas. Importantly, these are the myofibroblasts of the trabecular and capsular areas that expressed high levels of POSTN within the spleen tissue. In addition, vascular smooth muscle cells also expressed POSTN. Through CFU-S12 assays, we showed that hematopoietic support potential of stroma in Postn-deficient splenic hematopoietic niche was defective. Overall, we demonstrate that POSTN–ITGAV interaction plays an important role in spleen lymphohematopoiesis.

Niche cells regulate primordial germ cell quiescence in response to basement membrane signaling

“…Alternatively, the BM could be so compromised in epi- 1(RNAi) larvae that normal mechanical cues are lost. Similar mechanisms have been reported in mammalian cells, where integrin αV signaling is need to maintain the quiescence of hematopoietic stem cells in the bone marrow and spleen, and integrin- mediated adhesion to osteopontin supports quiescence of disseminated acute lymphoblastic leukemia cells (Mehatre et al, 2021, Khurana et al, 2016, Horton et al, 2020, Boyerinas et al, 2013). A distinct possibility is that laminin knock down liberates perlecan from the BM.…”

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

“…It was reported to be differentially expressed in the HSC population ( Umemoto et al., 2006 ) ( Umemoto et al., 2008 ), which we later showed was important for the regulation of proliferative activity in adult HSCs ( Khurana et al., 2016 ). We extended these studies and recently reported that Postn-Itgav interaction plays a role in the function of splenic HSC function ( Mehatre et al., 2021 ). Furthermore, this study showed the involvement of POSTN in splenic HSC niche formation as Postn -deletion led to reduced support for the incoming HSCs in spleen, upon transplantation.…”