Niche mediated integrin signaling supports steady state hematopoiesis in 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. Here, we examined the role of POSTN-ITGAV axis in lympho-hematopoietic activity in spleen that hosts rare population of HSCs, the functional regulation of which is not clearly known. Vav-iCre mediated deletion of Itgav in hematopoietic system led to higher proliferation rates, resulting in increased frequency of primitive HSCs in 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 increase in the spleen trabecular areas. Surprisingly, these were 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 important role in spleen lympho-hematopoiesis.

CFU-S assay: a historical single-cell assay that offers modern insight into clonal hematopoiesis

“…The CFU-S assay is also used to study extramedullary hematopoiesis in the splenic environment. For example, Mehatre et al [46] investigated the role of periostin (POSTN)−integrin-av signaling in splenic HSC function by transplanting healthy BM cells into wild-type or Postn knockout (KO) mice and compared the number of spleen colonies at day 12. They observed a significant decrease in the number of spleen colonies in Postn KO mice, suggesting that the POSTN-deficient splenic microenvironment may not be able to support either the homing and/or growth of hematopoietic progenitors.…”