Adrenal extramedullary hematopoiesis as an inducible model of the adult hematopoietic niche

Abstract

Hematopoietic Stem and Progenitor Cells (HSPCs) reside in the hematopoietic niche, a structure that regulates the balance of cellular quiescence, self-renewal and commitment in a demand-adapted manner. The bone marrow (BM) hematopoietic niche is formed by several cellular players, mainly endothelial cells, osteoblasts, adipocytes, and stromal cells. While the BM niche forms a complex structure, evidence exists for simpler, albeit functional, extramedullary hematopoietic niches. However, the composition of what constitutes the simplest unit of an HSPC supportive microenvironment remains largely unknown. Here, we show that the adult adrenal gland can be transformed into a hematopoietic supportive environment. Upon splenectomy and hormonal stimulation, the adult adrenal gland can be induced to recruit and host HSPC function, including serial transplantation. Furthermore, the adrenal stroma contains a CXCL12+ population, reminiscent of BM CXCL12-Abundant Reticular (CAR) cells. Mirroring this, we found CXCL12+ cells in patient samples obtained from a local cohort of myelolipoma, a benign adrenal tumor composed of adipose and hematopoietic tissue that constitutes the most common site of extramedullary hematopoiesis specific to the adult. We present our model as a novel tool to increase our understanding of the physiology of hematopoietic support and to facilitate the development of a boneless niche model.