Characterization of primitive marrow CD34+ cells that persist after a sublethal dose of total body irradiation

Exp Hematol. 2005 Nov;33(11):1388-401. doi: 10.1016/j.exphem.2005.07.010.

Abstract

Knowledge of the molecular events that occur during hematopoietic stem/progenitor cell (HSPC) development is vital to our understanding of blood cell production. To study the functional groups of genes characteristic of HSPCs we isolated a subpopulation of CD34+ bone marrow (BM) cells from nonhuman primates that persisted in vivo after a sublethal dose of total body irradiation (TBI). CD34+ cells isolated during the phase of maximal hematopoietic suppression show a transcriptional profile characteristic of metabolically inactive cells, with strong coordinate downregulation of a large number of genes required for protein production and processing. Consistent with this profile, these CD34+ cells were not able to generate hematopoietic colonies. Transcriptional profiling of these CD34+ cells in conjunction with a pathway analysis method reveals several classes of functionally related genes that are upregulated in comparison to the CD34+ cells obtained prior to TBI. These families included genes known to be associated with self-renewal and maintenance of HSPCs (including bone morphogenetic proteins), resistance to apoptosis (Bcl-2) as well as genes characteristic of a variety of nonhematopoietic tissues (gamma-aminobutyric acid/glycine receptor, complement receptor C1qRp). In contrast, during the period of hematopoietic recovery, the CD34+ cells expressed higher level of genes encoding factors regulating maturation and differentiation of HSPCs. Our data indicate that the primitive BM CD34+ cell population that persists after radiation possesses a transcriptional profile suggestive of pluripotency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / radiation effects*
  • Cell Survival
  • Gene Expression Profiling*
  • Gene Expression Regulation / radiation effects
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / radiation effects
  • Papio
  • Pluripotent Stem Cells / cytology
  • Transcription, Genetic / radiation effects
  • Whole-Body Irradiation*

Substances

  • Antigens, CD34