Roles of retinoids and retinoic Acid receptors in the regulation of hematopoietic stem cell self-renewal and differentiation

Abstract

Multipotent hematopoietic stem cells (HSCs) sustain blood cell production throughout an individual's lifespan through complex processes ultimately leading to fates of self-renewal, differentiation or cell death decisions. A fine balance between these decisions in vivo allows for the size of the HSC pool to be maintained. While many key factors involved in regulating HSC/progenitor cell differentiation and cell death are known, the critical regulators of HSC self-renewal are largely unknown. In recent years, however, a number of studies describing methods of increasing or decreasing the numbers of HSCs in a given population have emerged. Of major interest here are the emerging roles of retinoids in the regulation of HSCs.

Figure 1

Hematopoietic stem cells (HSCs) undergo fate decisions including self-renewal (resulting in the production of more HSCs), differentiation (producing more mature progenitor cells), senescence, or apoptosis, the latter two resulting in cell death.

Figure 2

A summary of the effects of ATRA on HSC-containing LKS+ cells. LTRC = long-term repopulating HSCs, STRC = short-term repopulating HSCs, CFU-S = colony-forming unit-spleen, CFC = colony-forming cell. Upward pointing arrows indicate increase in potential, the number of arrows indicates the magnitude of increase, sideways arrows indicate maintenance of potential. Modified from [25].