Steel factor affects SCL expression during normal erythroid differentiation

Abstract

Steel factor is one of the growth factors that controls the proliferation and differentiation of hematopoietic cells and SCL, also known as Tcl-5 or Tal-1, is a transcription factor involved in erythropoiesis. In this report, we studied the role of SCL in the proliferation of human peripheral blood burst-forming unit-erythroid (BFU-E) and the effects of Steel factor on SCL expression in proliferating erythroid cells. BFU-E-derived colonies increase progressively in size, as determined by cell number, from day 7 to day 14 of culture, with the greatest increase in colony size (10-fold expansion) occurring between day 7 and day 10. SCL protein levels in BFU-E-derived cells were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture, suggesting an association of SCL with erythroid proliferation. In contrast, SCL mRNA levels did not decrease significantly between day 7 and day 14 cells, suggesting that posttranscriptional mechanisms are largely responsible for the decrease in SCL protein observed. The role of SCL in Steel factor-induced erythroid proliferation was then examined. In BFU-E- derived colonies cultured with Steel factor, colony size was significantly increased compared to control. In day 7 and day 10 erythroid precursors cultured with Steel factor, SCL protein was increased significantly compared to control. The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests one mechanism through which Steel factor may enhance normal erythroid proliferation. SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation, suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel.

Transcription Factor SCL Is Required for c-kit Expression and c-Kit Function in Hemopoietic Cells

“…The expression pattern of SCL in primary hemopoietic cells parallels that of c-kit ( 8 ), suggesting that SCL functions in concert with c-Kit. Furthermore, a two- to fourfold augmentation of SCL protein was observed in maturing erythroid progenitors stimulated with SF ( 16 ). However, it is not known whether upregulation of SCL is a cause or consequence of c-Kit activation, cell survival, or cell proliferation.…”

In Vitro Proliferation and Differentiation of Erythroid Progenitors of Cord Blood

“…The difference in hemoglobin accumulation was the least at day 14 and at a maximum at day 18. The same authors [5] demonstrated decreased expression of β-globin mRNA in the erythroid cells cultured with SCF + EPO compared to cultures with EPO alone. These observations support that the decrease in the hemoglobin concentration may be due to inhibition of maturation rather than maturation delay.…”

“…On the other hand, Miller et al . [5] showed that SCF failed to increase the number of colonies derived from BFU‐E in adult peripheral blood in combination with EPO compared to EPO alone. In selected experiments, we made preliminary observations that the addition of SCF to EPO resulted in an increase in number of CFU‐E but not of BFU‐E (data not shown).…”

“…Stem cell factor (SCF) has been identified and determined to be a ligand of c-kit oncogene product [1] and has been cloned [2]. SCF has been reported to be the stimulator for pluripotent stem cells and synergizes with other cytokines in its stimulating effect [3], but this factor also appears to enhance more mature progenitor cell proliferation and differentiation [4][5][6][7][8][9][10]. It is still unclear how SCF exerts its function in the proliferation and differentiation of more mature progenitor cells.…”

Mitogen-activated protein kinase mediates erythropoietin-induced phosphorylation of the TAL1/SCL transcription factor in murine proerythroblasts

“…Similarly, expression of a full-length TAL1 cDNA potentiated erythroid differentiation of a human leukaemia cell line [32] and increased erythroid colony formation by normal human bone-marrow cells [33], whereas treatment of haematopoietic progenitors with a TAL1 antisense oligonucleotide led to a reduction in the number of erythroid colonies [34]. Finally, two growth factors important for erythroid differentiation, erythropoietin (Epo) and stem-cell factor, were both found to induce TAL1 expression [13,35].…”