Developmental regulation of erythropoiesis by hematopoietic growth factors: analysis on populations of BFU-E from bone marrow, peripheral blood, and fetal liver

Abstract

Fetal hematopoiesis is characterized by expanding erythropoiesis to support a continuously increasing RBC mass. To explore the basis for this anabolic, nonhomeostatic erythropoiesis, the proliferative effect of recombinant hematopoietic growth factors on highly enriched hematopoietic progenitor cells from fetal and adult tissues were compared. Fetal hepatic BFU-E, unlike adult bone marrow (BM) or peripheral blood (PB) BFU-E, were capable of proliferating in response to erythropoietin in the absence of added GM colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and erythropoietin (Epo) directly stimulated the expansion of the fetal BFU-E pool in suspension culture. A murine monoclonal antibody (MoAb), Ep 3, was raised against enriched fetal liver progenitor cells, which detected all fetal BFU-E and which reacted with the erythropoietin-responsive, GM-CSF/IL-3-independent fraction of adult BM BFU-E and CFU-E. All adult PB BFU-E were Ep 3- but became Ep 3+ after stimulation with GM-CSF or IL-3. These data indicate that Epo plays a unique role in fetal hepatic erythropoiesis, stimulating proliferation of immature BFU-E in addition to promoting terminal differentiation of later erythroid progenitor cells. In addition, these results demonstrate a MoAb which detects all erythropoietin-responsive progenitor cells and distinguishes the BFU-E compartments in adult BM and PB.

Transitional change of colony stimulating factor requirements for erythroid progenitors

“…This report presents direct evidence to support this hypothesis and also indicates that CSF requirement is one of the differentiation markers of immature erythroid pro enitors. In require IL-3 or GM-CSF for clonal development (Emerson et al, 1989;Valtieri et al, 1989). Based on the results presented here, it is most likely that the different requirement of these CSFs for erythroid development represents mainly a different stage of maturation of these cells.…”

“…Since the information available from the experimental colony assays represents a narrow stage of biological events of 0 1991 WILEY-LISS, INC. these cells, the dynamic events during the proliferation and differentiation of BFU-E to CFU-E have not yet been completely clarified. There is evidence that indicates the existence of BFU-E which require only EP for erythroid burst formation (Emerson et al, 1989;Valtieri et al, 1989). However, the reason for this is unclear.…”

Macrophage‐associated erythropoiesis and lymphocytopoiesis in mouse fetal liver: ultrastructural and ISH analysis

“…In mice, it arises initially in the blood island of the yolk sac and aortaegonade mesonephros region and shifts to the fetal liver (FL) on embryonic day (E) 12.5 (Medvinsky and Dzierzak, 1996;Mu¨ller et al, 1994). FL is an organ of transient hematopoietic activity during mid-gestation, with erythropoiesis being predominant during days 11e16 (Emerson et al, 1989). In addition, myeloid and B-cell precursors sequentially increase in the FL from day 13 to birth.…”

Inhomogeneity of the circulating BFU‐E regulation in sickle cell anaemia: accessory cells properties and BFU‐E growth factor response pattern

“…These data, taken as a whole. support the concept that the BFU-E population is heterogeneous, and that different BFU-E subsets may be engaged in the haemopoietic pathway under various physiological (Sieff et al, 1986;Emerson et al, 1989) or pathological circumstances, including degrees of severity within the same disease (Table 111).…”