Hematopoietic stem and progenitor cells (HSPCs) give rise to all cell types of the hematopoietic system through various processes, including asymmetric divisions. However, the contribution of stromal cells of the hematopoietic niches in the control of HSPC asymmetric divisions remains unknown. Using polyacrylamide microwells as minimalist niches, we show that specific heterotypic interactions with osteoblast and endothelial cells promote asymmetric divisions of human HSPCs. Upon interaction, HSPCs polarize in interphase with the centrosome, the Golgi apparatus, and lysosomes positioned close to the site of contact. Subsequently, during mitosis, HSPCs orient their spindle perpendicular to the plane of contact. This division mode gives rise to siblings with unequal amounts of lysosomes and of the differentiation marker CD34. Such asymmetric inheritance generates heterogeneity in the progeny, which is likely to contribute to the plasticity of the early steps of hematopoiesis.

Author contributions

Conceptualization: M.T., S.B.; Methodology: A.C., B.V., L.F., M.T., S.B.; Validation: L.B., M.T., S.B.; Formal analysis: A.C., B.V., M.G., M.T., S.B.; Investigation: A.C., B.V., S.B.; Resources: L.F., J.L.; Data curation: A.C.; Writing - original draft: A.C., M.T., S.B.; Writing - review & editing: A.C., M.T., S.B.; Visualization: M.T., S.B.; Supervision: L.B., M.T., S.B.; Project administration: M.T., S.B.; Funding acquisition: J.L., L.B., M.T.

Diversity and inclusion

We support inclusive, diverse and equitable conduct of research.

Funding

This work was supported by the European Research Council [Consolidator Grant 771599 (ICEBERG) to M.T. and Advanced Grant 741773 (AAA) to L.B.], the Fondation Bettencourt Schueller, the Emergence program of the Ville de Paris and the Fondation Schlumberger pour l'Education et la Recherche. A.C. received a PhD fellowship from the Fondation pour la Recherche Médicale (FDT20170437071).

Data availability

All relevant data can be found within the article and its supplementary information.

You do not currently have access to this content.