Characterization of bone marrow niches to support hematopoiesis, with important implications in regenerative medicine and in the study of the mechanisms of resistance to treatment of malignant hemopathies
There are specialized cells in the bone marrow called stromal cells, that support the development of hematopoietic cells by producing specific growth factors. Chemokine CXCL12 and cytokine IL7 are essential for early B-cell differentiation (pro-B), whereas hematopoietic stem cell (HSC) maintenance is dependent on CXCL12 and SCF growth factor. The diversity of stromal cells and the mechanisms that allow hematopoietic cells to interact with their specific stromal niche remain poorly understood. A study by Stéphane Mancini and his colleagues at the CRCM published in the Journal Cell Reports describes the characterization of stromal cells that allow the development of pro-B cells and identifies the interaction network responsible for their specific retention in their niche.
This study shows the existence of preferential contacts between pro-B cells and peri-sinusoidal stromal cells (CSPS) in mice. While the CSPS were known for their ability to support CSH self-renewal through the expression of factors such as CXCL12 and SCF, this study shows that they also express genes needed for B lymphocyte development such as IL-7. In addition, pro-B cells are frequently located near CSH in the same niche indicating that CSPS are able to simultaneously support the processes of self-renewal and differentiation.
By a bioinformatic analysis, this study made it possible to identify the molecules allowing the interactions between the pro-B cells and the CSPS among which Nidogen-1, whose essential role for the retention of the pro-B cells in their niche was confirmed in mice deficient for this protein. Finally, pro-B cells and hematopoietic progenitors have also been localized in humans in the vicinity of stromal cells with similar characteristics and secreting IL7 and CXCL12.
Therefore, these results show that in mice and humans, there is a multi-specific niche capable of supporting both the development of multipotent progenitors and also of cells permanently involved in their hematopoietic lineage, thus calling into question the multiplicity of hematopoietic niches in the bone marrow. This understanding of the niches and the mechanisms allowing them to support hematopoiesis has important implications in regenerative medicine as well as in the study of the phenomena involved in resistance to the treatment of malignant hemopathies.
Nidogen-1 contributes to the interaction network involved in pro B cell retention in the perisinusoidal hematopoietic stem cell niche.
Balzano M, De Grandis M, Vu-Manh T-P, Chasson L, Bardin F, Farina A, Sergé A, Bidaut G, Charbord P, Herault, Bailly A-L, Michaud Cartier A, Boned A, Dalod M, Duprez E, Genever P, Coles M, Bajenoff M, Xerri L, Aurrand-Lions M, Schiff C & Mancini S
Cell Reports 2019 doi 10.1016/j.celrep.2019.02.065