heterotypic interaction promotes asymmetric division of human hematopoietic stem and progenitor cells

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 heterotypic interaction with osteoblast promotes asymmetric division of human HSPC. Upon interaction, HSPCs polarize in interphase with 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 gives rise to siblings with unequal amounts of lysosomes and differentiation markers such as CD34. Such asymmetric inheritance generates heterogeneity in the progeny, which is likely to be a key contributor to the plasticity of the early steps of hematopoiesis.