Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis.

Tropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked ( ) with human blood trait variation. Prior work suggested that regulated blood cell formation in vitro, but it was unclear how or when affected hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, knockout was found to augment developmental cell state transitions, as well as TNFα and GTPase signaling pathways, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses showed decreased expression during human HE specification, suggesting that regulated in vivo hematopoiesis via similar mechanisms. Indeed, analyses of a gene trap mouse model showed that deficiency enhanced the formation of HE during embryogenesis. These findings illuminate novel effects of on developmental hematopoiesis.