Cellular Basis of Embryonic Hematopoiesis and Its Implications in Prenatal Erythropoiesis.

Toshiyuki Yamane

doi:10.3390/ijms21249346

Abstract

Primitive erythrocytes are the first hematopoietic cells observed during ontogeny and are produced specifically in the yolk sac. Primitive erythrocytes express distinct hemoglobins compared with adult erythrocytes and circulate in the blood in the nucleated form. Hematopoietic stem cells produce adult-type (so-called definitive) erythrocytes. However, hematopoietic stem cells do not appear until the late embryonic/early fetal stage. Recent studies have shown that diverse types of hematopoietic progenitors are present in the yolk sac as well as primitive erythroblasts. Multipotent hematopoietic progenitors that arose in the yolk sac before hematopoietic stem cells emerged likely fill the gap between primitive erythropoiesis and hematopoietic stem-cell-originated definitive erythropoiesis and hematopoiesis. In this review, we discuss the cellular origin of primitive erythropoiesis in the yolk sac and definitive hematopoiesis in the fetal liver. We also describe mechanisms for developmental switches that occur during embryonic and fetal erythropoiesis and hematopoiesis, particularly focusing on recent studies performed in mice.

Highlights

Erythrocytes are observed in jawed vertebrates and jawless fishes [1]
After the first wave of erythropoiesis and hematopoiesis, hematopoietic stem cells generated at multiple sites, including the aorta, placenta, and yolk sac, migrate into the fetal liver
Embryonic and fetal hematopoiesis do not occur in simple two-step phases of primitive erythropoiesis and definitive hematopoiesis

Summary

Introduction

Erythrocytes are observed in jawed vertebrates and jawless fishes (lampreys and hagfish) [1]. In the mid-gestational stage, ζ, εy, and βH1 globin genes are silenced and replaced by α, βmajor, and βminor globins [6,7] These late-fetal/adult globin genes continue to be expressed throughout life. It is known that globin molecules expressed only during embryonic and fetal life have higher affinity for oxygen compared to adult globins, which presumably allows for efficient maternal–embryonic gas exchange in the placental environment [8] In this decade, pathbreaking studies have uncovered molecules involved in globin-switching. It was revealed that transcription factors BCL11A and ZBTB7A ( known as LRF) play pivotal roles in repressing embryonic/fetal globin expression in both humans and mice [9,10,11,12]. We briefly describe human embryonic and fetal erythropoiesis at the end of this review

Features of Primitive Erythropoiesis

Erythropoiesis and Hematopoiesis in the Fetal Liver

Embryonic and Fetal Erythropoiesis in Humans

Findings

Conclusions