Minireview: Nuclear receptors, hematopoiesis, and stem cells

Abstract

Nuclear receptors (NRs) regulate a panoply of biological processes, including the function and development of cells within the hematopoietic and immune system, such as erythrocytes, monocytes, and lymphocytes. Significantly less is known regarding the function of NRs in regulating the fate of hematopoietic stem cells (HSCs), the self-renewing, pluripotent cells that give rise to the entirety of the blood and immune systems throughout the lifetime of an individual. Several recent studies suggest, either directly or indirectly, a role for members of the NR family in regulating the differentiation and self-renewal of HSCs, embryonic stem cells, and induced pluripotent stem cells. Herein, we review in detail the function of specific NRs in controlling HSC and other stem cell fate and propose a framework through which these observations can be translated into therapeutic amplification of HSCs for clinical purposes.

Figure 1

Overview of the hematopoietic hierarchy. The spectrum of hematopoietic stem and progenitor cells and their progeny are represented along with the phenotype and functional assays used to characterize the stem and progenitor cell pool. LTHSC, Long-term repopulating hematopoietic stem cell; STHSC, short-term repopulating hematopoietic stem cell; MPP, multipotent progenitor cell; CMP, common myeloid progenitor cell; MEP, megakaryocyte-erythroid progenitor cell; GMP, granulocyte monocyte progenitor cell; CLP, common lymphoid progenitor cell; RBC, red blood cell; 34-KLS, CD34- c-kit+lineage- sca-1+ cells; CRU, competitive repopulating unit assay; CFU-Spleen, colony forming unit-spleen assay; CFC, colony-forming cell assay, d 14.

Figure 2

Schematic overview of major HSC self-renewal pathways. The most well-characterized signaling pathways and transcription factors involved in regulating HSC self-renewal are shown. BMP, Bone morphogenetic protein; NICD, notch intracellular domain; RBPJ, recombinant signal binding protein; LEF, lymphoid enhancer binding protein; GFI-1, growth factor independent 1; HOX, homeobox proteins.

Figure 3

Schematic overview of NR regulation in hematopoiesis. NRs that have activating function are shown in green and repressive actions are shown in red. LTHSC, long-term repopulating hematopoietic stem cell; STHSC, short-term repopulating hematopoietic stem cell; MPP, multipotent progenitor cell; CMP, common myeloid progenitor cell; MEP, megakaryocyte-erythroid progenitor cell; GMP, granulocyte-monocyte progenitor cell; CLP, common lymphoid progenitor cell; RBC, red blood cell.