Apoptosis of human erythroid colony-forming cells is decreased by stem cell factor and insulin-like growth factor I as well as erythropoietin

J Cell Physiol. 1993 Aug;156(2):264-71. doi: 10.1002/jcp.1041560207.


To clarify the manner by which erythropoietin (EP), stem cell factor (SCF), or insulin-like growth factor I (IGF-I) regulate erythropoiesis, apoptosis of human erythroid progenitor cells was investigated. Human burst-forming units-erythroid (BFU-E) partially purified from peripheral blood were cultured for 6 days to generate erythroid colony-forming cells (ECFC), which consist mainly of colony-forming units-erythroid (CFU-E). The cells were labeled with [3H]thymidine, incubated in serum-free liquid media, at 37 degrees C, for 16 h, and the pattern of DNA breakdown was analyzed by agarose gel electrophoresis. When these cells were incubated without EP, 70% of the total cellular DNA was broken down into DNA fragments of less than 5 kilobases and nuclear condensation and fragmentation, characteristic of apoptosis, were evident. While EP greatly reduced the amount of DNA breakdown to 23%, SCF and IGF-I each reduced the amount of DNA breakdown to 38-46% and, when added together, to 24%. Dose-response experiments with SCF and IGF-I showed a dose-dependent reduction in DNA fragmentation at concentrations that stimulate colony formation in serum-free semisolid cultures. Finally, assays of ECFC performed by the plasma clot method, after serum-free liquid culture, at 37 degrees C, for 16 h, demonstrated marked protection of erythroid colony-forming capacity by SCF or IGF-I in the absence of EP, as well as by EP itself. These data indicate that human erythroid progenitor cells undergo apoptosis which is reduced by SCF and IGF-I as well as EP and suggest that the control of apoptosis by each of these factors has a prominent role in the regulation of erythropoiesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Division
  • Cells, Cultured
  • Culture Media, Serum-Free / pharmacology
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Erythroid Precursor Cells / cytology*
  • Erythroid Precursor Cells / metabolism
  • Erythroid Precursor Cells / physiology
  • Erythropoiesis / physiology
  • Erythropoietin / pharmacology*
  • Erythropoietin / physiology
  • Hematopoietic Cell Growth Factors / pharmacology*
  • Hematopoietic Cell Growth Factors / physiology
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor I / physiology
  • Stem Cell Factor
  • Thymidine / metabolism
  • Tritium


  • Culture Media, Serum-Free
  • Hematopoietic Cell Growth Factors
  • Stem Cell Factor
  • Tritium
  • Erythropoietin
  • Insulin-Like Growth Factor I
  • DNA
  • Thymidine