Characterization of primitive marrow CD34+ cells that persist after a sublethal dose of total body irradiation.
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.
Mahmud
Nadim
N
University of Illinois College of Medicine, Chicago, IL 60607, USA. nadim@uic.edu
Rose
David
D
Pang
Wenxin
W
Walker
Russell
R
Patil
Veena
V
Weich
Nadine
N
Hoffman
Ronald
R
D000818:Animals; D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000166:cytology / Q000528:radiation effects*; D002470:Cell Survival; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D010215:Papio; D039904:Pluripotent Stem Cells / Q000166:cytology; D014158:Transcription, Genetic / Q000528:radiation effects; D014916:Whole-Body Irradiation
D018952:Antigens, CD34