Session
21
Oral presentations Experimental hematology / oncology
Nov. 20, 2024,
1:45 p.m. - 3:15 p.m.,
Shanghai 1-2
Abstract
3
Inducible CXCL12/CXCR4-dependent extramedullary hematopoietic niches in the adrenal gland
F. Schyrr1, A. Alonso-Calleja1, A. Vijaykumar2, J. Sordet-Dessimoz1, S. Gebhard1, R. Sarkis1, C. Bataclan1, S. Ferreira Lopes1, A. Oggier1, L. de Leval1, C. Nombela-Arrieta2, O. Naveiras1, Presenter: F. Schyrr1 (1Lausanne, 2Zurich)
Objective
Adult hematopoietic Stem and Progenitor Cells (HSPCs) reside in the bone marrow hematopoietic niche, which regulates HSPC quiescence, self-renewal, and commitment in a demand-adapted manner. While the complex bone marrow niche is responsible for adult haematopoiesis, evidence exists for simpler, albeit functional and more accessible, extramedullary hematopoietic niches. Inspired by the anecdotal description of retroperitoneal hematopoietic masses occurring at higher frequency upon hormonal dysregulation within the adrenal gland, we hypothesized that the adult adrenal gland could be induced into a hematopoietic supportive environment in a systematic manner, thus revealing mechanisms underlying de novo niche formation.
Methods
Using a strategy combining splenectomy and hormonal stimulation in mice (ACTH, testosterone and G-CSF), we induced blood cell recruitment in the adrenal gland and functionally tested haematopoiesis through colony forming assays, serial transplantation and immunostaining signs of in situ haematopoiesis as well as niche remodelling. We validated our findings in human myelolipoma, a benign tumour composed of adipose and hematopoietic tissue.
Results
We showed that the adult adrenal gland of mice can be induced to recruit and host functional HSPCs, capable of serial transplantation, and that this phenomenon is associated with de novo formation of platelet-derived growth factor receptor α (PDGFRα) expressing stromal nodules. We further showed that adrenal glands contain a stromal population reminiscent of the CXCL12-Abundant Reticular (CAR) cells, which are key in the bone marrow HSPC niche. Mechanistically, HSPC homing to hormonally-induced adrenal glands was found to be dependent on the CXCR4/CXCL12 axis. Mirroring our findings in mice, we found reticular CXCL12+ cells co-expressing FOXC1, a master regulator of the niche, in primary samples from human adrenal myelolipomas.
Conclusion
The adrenal gland can be hormonally induced to host HSPCs in adult mice. Furthermore, adrenal extramedullary haematopoiesis is associated to the formation of PDGFRα+LepR+/- foci in mice and CXCL12+FOXC1+ stroma in humans. Our findings reignite long-standing questions regarding hormonal regulation of haematopoiesis and provide a novel model to facilitate the study of adult-specific inducible hematopoietic niches which may pave the way to therapeutic applications.