Abstract
Embryonic and adult hematopoiesis are both finely regulated by a number of signaling mechanisms. In the mammalian embryo, short-term and long-term hematopoietic stem cells (HSC) arise from a subset of endothelial cells which constitute the hemogenic endothelium. These HSC expand and give rise to all the lineages of blood cells in the fetal liver, first, and in the bone marrow from the end of the gestation and throughout the adult life. The retinoic acid (RA) signaling system, acting through the family of nuclear retinoic acid receptors (RARs and RXRs), is involved in multiple steps of the hematopoietic development, and also in the regulation of the differentiation of some myeloid lineages in adults. In humans, the importance of this RA-mediated control is dramatically illustrated by the pathogeny of acute promyelocytic leukemia, a disease produced by a chromosomal rearrangement fusing the RARa gene with other genes. The aberrant fusion protein is able to bind to RARα target gene promoters to actively suppress gene transcription. Lack of function of RARα leads to a failure in the differentiation of promyelocytic progenitors. In this review we have collected the available information about all the phases of the hematopoietic process in which RA signaling is involved, being essential for steps such as the emergence of HSC from the hemogenic endothelium, or modulating processes such as the adult granulopoiesis. A better knowledge of the RA-mediated signaling mechanisms can contribute to the knowledge of the origin of many pathologies of the hematopoietic system and can provide new clinical avenues for their treatment.
Highlights
Adult hematopoiesis is the complex process of generation of blood cells from multipotent progenitors
In this paper, which forms part of a special issue of Journal of Developmental Biology devoted to the developmental mechanisms regulated by retinoids, we will review the current knowledge about how retinoic acid (RA) is critically involved in both, embryonic and adult hematopoiesis
This study suggests a role for RAR in human hematopoietic stem cells (HSC) different to that described in mice
Summary
Adult hematopoiesis is the complex process of generation of blood cells from multipotent progenitors. Embryonic hematopoiesis originates both the early cohorts of blood cells necessary for proper development and the long term HSC [4,5]. Differentiation of blood cells and HSC from the mesoderm, from the hemogenic endothelium through an endothelial-hematopoietic transition (EHT), requires fine regulation by a number of signaling mechanisms [6]. In this paper, which forms part of a special issue of Journal of Developmental Biology devoted to the developmental mechanisms regulated by retinoids, we will review the current knowledge about how retinoic acid (RA) is critically involved in both, embryonic and adult hematopoiesis. We will pay special attention to the developmental processes in which RA is playing a function for differentiation of long term HSC. We will describe how a failure in the RA-mediated signaling mechanisms can originate severe pathologies of the hematopoietic system in humans
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