Inducible CXCL12/CXCR4-dependent extramedullary hematopoietic niches in the adrenal gland.
Details
Serval ID
serval:BIB_608A40306195
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inducible CXCL12/CXCR4-dependent extramedullary hematopoietic niches in the adrenal gland.
Journal
Blood
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
29/08/2024
Peer-reviewed
Oui
Volume
144
Number
9
Pages
964-976
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Adult hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) hematopoietic niche, which regulates HSPC quiescence, self-renewal, and commitment in a demand-adapted manner. Although the complex BM niche is responsible for adult hematopoiesis, 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 in the adult. Here, we show that upon splenectomy and hormonal stimulation, 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/leptin receptor (PDGFRα+/LEPR+/-)-expressing stromal nodules. We further show in CXCL12-green fluorescent protein reporter mice that adrenal glands contain a stromal population reminiscent of the CXCL12-abundant reticular cells, which compose the BM HSPC niche. Mechanistically, HSPC homing to hormonally induced adrenal glands was found dependent on the CXCR4-CXCL12 axis. Mirroring our findings in mice, we found reticular CXCL12+ cells coexpressing master niche regulator FOXC1 in primary samples from human adrenal myelolipomas, a benign tumor composed of adipose and hematopoietic tissue. Our findings reignite long-standing questions regarding hormonal regulation of hematopoiesis and provide a novel model to facilitate the study of adult-specific inducible hematopoietic niches, which may pave the way to therapeutic applications.
Keywords
Animals, Receptors, CXCR4/metabolism, Receptors, CXCR4/genetics, Chemokine CXCL12/metabolism, Mice, Hematopoietic Stem Cells/metabolism, Hematopoietic Stem Cells/pathology, Adrenal Glands/metabolism, Adrenal Glands/pathology, Stem Cell Niche, Mice, Inbred C57BL, Humans, Receptor, Platelet-Derived Growth Factor alpha/metabolism, Receptor, Platelet-Derived Growth Factor alpha/genetics, Receptors, Leptin/metabolism, Receptors, Leptin/genetics, Hematopoiesis, Extramedullary, Splenectomy, Mice, Transgenic
Pubmed
Open Access
Yes
Create date
13/05/2024 8:28
Last modification date
05/09/2024 10:00