Developmental changes in hematopoietic stem cell properties

Hematopoietic stem cells (HSCs) comprise a rare population of cells that can regenerate and maintain lifelong blood cell production. This functionality is achieved through their ability to undergo many divisions without activating a poised, but latent, capacity for differentiation into multiple blood cell types. Throughout life, HSCs undergo sequential changes in several key properties. These affect mechanisms that regulate the self-renewal, turnover and differentiation of HSCs as well as the properties of the committed progenitors and terminally differentiated cells derived from them. Recent findings point to the Lin28b-let-7 pathway as a master regulator of many of these changes with important implications for the clinical use of HSCs for marrow rescue and gene therapy, as well as furthering our understanding of the different pathogenesis of childhood and adult-onset leukemia. Hematopoetic stem cells (HSCs), which give rise to all the blood lineages in the body, change throughout mammalian development. In a review article, Michael Copley and Connie Eaves from the British Columbia Cancer Agency in Vancouver, Canada, discuss the molecular pathways involved in controlling the switch from fetal to adult HSCs. They note that the Lin28b-let-7 pathway acts as a master regulator of this postnatal transition. This pathway could therefore serve as a target for therapeutic applications. For example, modulating the expression of the Lin28b-let-7 pathway or its downstream targets could be a useful strategy to improve outcomes in patients undergoing gene therapy for certain blood disorders, such as X-linked severe-combined immunodeficiency. The Lin28b-let-7 pathway is also likely to be involved in the formation of childhood- and adult-onset leukemias so could yield insights into disease onset.