TY - JOUR TI - Microtubules control nuclear shape and gene expression during early stages of hematopoietic differentiation AU - Biedzinski, Stefan AU - Agsu, Gökçe AU - Vianay, Benoit AU - Delord, Marc AU - Blanchoin, Laurent AU - Larghero, Jerome AU - Faivre, Lionel AU - Théry, Manuel AU - Brunet, Stéphane T2 - The EMBO Journal AB - Abstract Hematopoietic stem and progenitor cells (HSPC) can differentiate into all hematopoietic lineages to support 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 HSPC differentiation has been intensively studied but our understanding of the potential contribution of inner cell architecture is relatively poor. Here, we show that large invaginations are generated by microtubule constraints on the swelling nucleus of human HSPC during early commitment toward the myeloid lineage. These invaginations are associated with a local reduction of lamin B density, local loss of heterochromatin H3K9me3 and H3K27me3 marks, and changes in expression of specific hematopoietic genes. This establishes the role of microtubules in defining the unique lobulated nuclear shape observed in myeloid progenitor cells and suggests that this shape is important to establish the gene expression profile specific to this hematopoietic lineage. It opens new perspectives on the implications of microtubule-generated forces, in the early commitment to the myeloid lineage. DA - 2020/10/22/ PY - 2020 DO - 10.15252/embj.2019103957 DP - embopress.org (Atypon) VL - n/a IS - n/a SP - e103957 J2 - The EMBO Journal SN - 0261-4189 UR - https://www.embopress.org/doi/abs/10.15252/embj.2019103957 Y2 - 2020/10/22/18:30:14 KW - chromatin remodeling KW - differentiation KW - microtubule KW - nucleus deformation KW - stem cells ER -