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

Abstract

AbstractTropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linkedTropomyosin 1(TPM1) with human blood trait variation. Prior work suggested thatTPM1regulated blood cell formation in vitro, but it was unclear how or whenTPM1affected hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems,TPM1knockout 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 decreasedTPM1expression during human HE specification, suggesting thatTPM1regulated in vivo hematopoiesis via similar mechanisms. Indeed, analyses of aTPM1gene trap mouse model showed thatTPM1deficiency enhanced the formation of HE during embryogenesis. These findings illuminate novel effects ofTPM1on developmental hematopoiesis.