Nidogen-1 Contributes to the Interaction Network Involved in Pro-B Cell Retention in the Peri-sinusoidal Hematopoietic Stem Cell Niche

In the bone marrow, CXCL12 and IL-7 are essential for B cell differentiation, whereas hematopoietic stem cell (HSC) maintenance requires SCF and CXCL12. Peri-sinusoidal stromal (PSS) cells are the main source of IL-7, but their characterization as a pro-B cell niche remains limited. Here, we characterize pro-B cell supporting stromal cells and decipher the interaction network allowing pro-B cell retention. Preferential contacts are found between pro-B cells and PSS cells, which homogeneously express HSC and B cell niche genes. Furthermore, pro-B cells are frequently located in the vicinity of HSCs in the same niche. Using an interactome bioinformatics pipeline, we identify Nidogen-1 as essential for pro-B cell retention in the peri-sinusoidal niche as confirmed in Nidogen-1−/− mice. Finally, human pro-B cells and hematopoietic progenitors are observed close to similar IL-7+ stromal cells. Thus, a multispecific niche exists in mouse and human supporting both early progenitors and committed hematopoietic lineages. [Display omitted] •Murine peri-sinusoidal stromal cells co-express HSC and early B cell niche genes•HSCs and early B cells form specific interaction networks with PSS cells•Nidogen-1 is involved in pro-B cell retention in the peri-sinusoidal niche•Stromal cells with similar characteristics are present in human bone marrow Balzano et al. show that bone marrow peri-sinusoidal stromal cells, which form the hematopoietic stem cell niche, also express B cell niche genes including IL-7 and Nidogen-1. Loss of Nidogen-1 expression specifically affects access of pro-B cells to IL-7, resulting in impaired expansion and differentiation of early B cells.