Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment

Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field allowed us analyze with single cell resolution implicate that functional heterogeneity may exist even within highly purified HSC compartment. However, due part technical limitations analyzing extremely rare populations our incomplete understanding biology, neither biological meaning why exists nor precise mechanism how is determined compartment entirely known. Here we show first evidence self-renewal capacity varies degree replication stress dose results Using Hoxb5-reporter mouse line which enables distinguish between long-term (LT)-HSCs short-term (ST)-HSCs, found ST-HSCs quickly lose under high environments but can low for long periods time. Critically, exogeneous Hoxb5 expression confers protection against loss Hoxb5-negative partially alter fate LT-HSCs. Our demonstrate imparts by regulating capacity. Additionally, Hoxb5-positive as fail-safe system protect from exhaustion throughout organism’s lifespan.