Stem cells maintain stemness and produce differentiated progeny by undergoing asymmetric cell divisions that differentially segregate cell-fate-determining factors to the two daughter cells. Discher and colleagues now investigate the roles of non-muscle myosin (MII) isoforms in regulating asymmetric cell division and differentiation of haematopoietic cells (Cell Stem Cell 14, 81–93; 2014).

The authors used mass-spectrometry-calibrated intracellular flow cytometry to demonstrate that human adult haematopoiesis involves a switch from the expression of both MIIB and MIIA isoforms to MIIA alone. They showed that MIIB is more membrane-polarized in CD34+ haematopoietic stem and progenitor cells (HSPCs) than MIIA, and localizes at the cleavage furrow during asymmetric cell division. MIIB segregated asymmetrically with the CD34+ progeny, and partial MIIB depletion blocked both MIIB asymmetric segregation and asymmetric cell division. MIIA did not exhibit asymmetric distribution, but was instead present in its phosphorylated, inactive form, and was activated by differentiation-inducing cytokines in a matrix-stiffness-dependent manner. Injection of MIIB-depleted CD34+ cells into the bone marrow of mice led to reduced peripheral blood cell levels, whereas genetic loss of MIIA suppressed the numbers of differentiated cells. Short-term blebbistatin-mediated inhibition of both isoforms enriched for HSPCs, whereas long-term inhibition blocked cell division and resulted in apoptosis of dividing CD34+ cells.

These findings highlight the distinct roles of MII isoforms in regulating haematopoiesis.