Nucleus deformation by microtubules during early steps of hematopoiesis

Cells from the myeloid and lymphoid lineages fulfill distinct functions with specific shapes and intra-cellular architectures. The role of cytokines in the regulation of HSC differentiation has been intensively studied but our understanding of the potential contribution of inner cell architecture is relatively poor. Here we studied the early commitment of human HSC and identified specific microtubule network rearrangements and nucleus shape changes that accompany cells differentiation toward the myeloid lineage. This work established the role of microtubules in the mechanical regulation of nucleus shape, chromatin architecture and HSC differentiation and open new perspectives in our appreciation of the implication of intra-cellular forces in the early specification of the myeloid lineage. We compared the transcriptome of HSCs differentiated for 3 days in normal culture medium, to the transcriptome of HSCs cultured in the same manner but treated with the dynein inhibitor ciliobrevin D (CILIO) or taxol (TX) between day 2 and day 3.