Development of pluripotent hematopoietic progenitor cells in the human fetus

Abstract

Pluripotent hematopoietic progenitor cells (CFU-GEMM), myeloid progenitor cells (CFU-GM), and erythroid progenitors (BFU-E) were studied in midtrimester human fetuses using the mixed colony assay. All three progenitor cell populations were detected at high levels in the fetal liver from 12 to 23 wk of gestation. Stem cells were first observed in the bone marrow at 15–16 wk of gestation, although bone marrow cultures from earlier fetuses showed heavy growths of stromal cells. Spleen cultures first showed growth of stem cells at 18–19 wk, but fetal thymus showed no hematopoietic activity. Peripheral blood from four fetuses aged 13, 18, 20, and 21 wk showed very high levels of all 3 progenitor cells. The results demonstrate that hematopoietic development in the human fetus parallels that of the mouse. The observation that stromal cell development in the bone marrow precedes the appearance of hematopoietic progenitor cells suggests that they may be closely involved in stem cell growth.

Molecular mechanisms underlying erythropoiesis: Cycling activity of adult BFU-e relates to their requirement for c-myb function and potential for HbF synthesis

“…Erythropoiesis and Hemoglobin Switching Normal blood cells are generated from a pool of stem cells capable of selfrenewal and differentiation into progenitors committed to the various hemopoietic lineages [l-31. Progenitors in turn proliferate and differentiate, thus giving rise to morphologically recognizable precursors and then terminally differentiated cells [4,5]. This cascade of events can be reproduced in vitro by hematopoietic colony formation in semisolid medium [l-31 via interaction of progenitor cells with specific growth factors [6-81. Two erythroid progenitors have been identified in the adult [9, 101 and the embryonic-fetal [11, 121 age: the erythroid burst-forming (BFU-e) and colonyforming units (CFU-e), which generate, respectively, large "bursts" and small clusters of erythroblasts.…”

Differential expression of lymphoid and myeloid markers on differentiating hematopoietic stem cells in normal and tumor-bearing adult human liver

“…[1][2][3][4][5][6][7][8][9][10] Hepatic hematopoiesis, in adult mice, has been shown to be important in the generation of antitumor effector cells. 6,7,11,12 While the hematopoietic function of the liver in the human fetus is well documented, 13 the role of the adult human liver (AHL) in hematopoiesis is thought to be relatively minor. However, the hematopoietic potential of the liver is retained in the adult human and can become activated as demonstrated by the extramedullary erythropoiesis that occurs in liver or spleen at times of severe bone marrow dysfunction.…”

Fetal haemopoietic cells display enhanced migration across endothelium

“…The establishment of haemopoiesis in diverse anatomical locations during embryonic and fetal life means that multipotent haemopoietic cells must circulate and continually migrate into extravascular fetal tissues. Early studies have reported the presence of haemopoietic progenitors in fetal blood, the numbers correlating inversely with gestational age, as would be expected (Hann et al, 1982;Linch et al, 1982). Such cells, in keeping with their physiological role and ontogenic status, may possess superior homing and migratory properties.…”