Involvement of H-ras in erythroid differentiation of TF1 and human umbilical cord blood CD34+++ cells

Yue Ge, Zhi Hua Li, Mark S. Marshall, Hal E. Broxmeyer, Li Lu

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

To investigate the role of the ras gene in erythroid differentiation, a human erythroleukemic cell line, TF1, was transduced with a selectable retroviral vector carrying a mammalian wild type H-ras gene or a cytoplasmic dominant negative RAS1 gene. Transduction of TF1 cells with the wild type H- ras gene resulted in changes of cell types and up-regulation of erythroid- specific gene expression similar to that seen in differentiating erythroid cells. The number of red blood cell containing colonies derived from TF1 cells transduced with wild type H-ras CDNA was significantly increased and the cells in the colonies were more hemoglobinized as estimated by a deeper red color compared to those colony cells from mock or dominant negative RAS1 gene transduced TF1 cells, suggesting increased erythroid differentiation of TF1 cells after transduction of wild type H-ras in vitro. The mRNA levels of β- and γ-, but not α-, globin genes were significantly higher in H-ras transduced TF1 cells than those in TF1 cells transduced with mock or dominant negative RAS 1 gene. Moreover, a 4kb pre-mRNA of the Erythropoietin receptor (EpoR) was highly expressed only in H-ras transduced TF1 cells. Additionally, human umbilical cord blood (CB) CD34+++ cells which are highly enriched for hematopoietic stem/progenitor cells were transduced with the same retroviral vectors to evaluate in normal primary cells the activities of H- ras in erythroid differentiation. Increased numbers of erythroid cell containing colonies (BFU-E and CFU-GEMM) were observed in CD34+++ cells transduced with the H-ras cDNA, compared to that from mock transduced cells. These data suggest a possible role for ras in erythroid differentiation.

Original languageEnglish (US)
Pages (from-to)124-136
Number of pages13
JournalBlood Cells, Molecules and Diseases
Volume24
Issue number2
DOIs
StatePublished - Jun 1998

Keywords

  • CD34
  • Cells
  • Cord Blood
  • Erythroid differentiation
  • H-ras
  • TF1 Cells

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

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