Asymmetric Cell Division (ACD)

How does asymmetric cell division (ACD) influence multilineage blood cell development (during homeostasis and stress)?

Most stem cell populations balance self-renewal with differentiation through control of cell division. Cell division is the process by which one “mother” cell produces two “daughter” cells. When both daughter cells maintain the identity of the original mother cell, this is considered a self-renewing symmetric cell division. In contrast, if the two daughter cells adopt two different cell fates, this is considered an asymmetric cell division (ACD). ACD is often used by stem cells to balance maintaining a pool of immature mother stem cells with producing daughter cells that can go on to become mature functional differentiated cells. 

Unlike other stem cell populations, we do not yet have direct in vivo evidence for ACD in HSCs nor a mechanistic understanding of how ACD impacts hematopoiesis in vivo. But, indirect and in vitro evidence suggests that ACD may play a role in balancing self-renewal with differentiation during hematopoiesis. Furthermore, studies have shown that mutations in proteins thought to be involved in ACD lead to premature HSC aging, bone marrow engraftment failure, and blood diseases such as acute myeloid leukemia (AML) and myeloproliferative disorders.

Decades of indirect evidence support the notion that ACD occurs during hematopoiesis, and yet, despite its fundamental importance, we lack direct evidence for ACD in vivo, as well as a mechanistic understanding of how it occurs or how signals from the hematopoietic microenvironment influence ACD. My research program aims to bridge this critical knowledge gap by utilizing Drosophila to develop mechanistic models of how ACD functions in hematopoiesis during both homeostasis and stress.