Anatomical compartments modify the response of human hematopoietic cells to a mitogenic signal.
Methods for specifically regulating transplanted cells have many applications in gene and cell therapy. We examined the response of human cord blood CD34+ cells to a specific mitotic signal in vivo. Using a conditional signaling molecule (F36VMpl) that is specifically activated by an artificial ligand called a chemical inducer of dimerization (CID), human hematopoietic cells transplanted into immune deficient mice were induced to proliferate. Only differentiating erythroid precursors and multipotential and erythroid progenitors (colony-forming unit [CFU]-mix and burst forming unitserythroid [BFUe]) responded; however, the nature of the response differed markedly between bone marrow and spleen. In the marrow, F36VMpl induced a 12- to 17-fold expansion of differentiated erythroid precursors and a loss of CFU-mix and BFUe. In the spleen, F36VMpl induced a marked rise in BFUe and CFU-mix and, relative to marrow, a much less prominent rise in more mature red cells. Clonal analysis was most consistent with the interpretation that the spleen and bone marrow differentially regulate the response of human progenitors to a mitotic signal, possibly influencing progenitor expansion versus differentiation. These findings establish CIDs as in vivo growth factors for human hematopoietic cells.
Nagasawa
Yasuo
Y
Department of Medicine, K260 Health Sciences Building, Mailstop 357710, University of Washington, Seattle, Washington 98195, USA.
Wood
Brent L
BL
Wang
Linlin
L
Lintmaer
Ingrid
I
Guo
Wenjin
W
Papayannopoulou
Thalia
T
Harkey
Michael A
MA
Nourigat
Cynthia
C
Blau
C Anthony
CA
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000033:anatomy & histology; D003114:Colony-Forming Units Assay; D004247:DNA / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008934:Mitogens / Q000494:pharmacology*; D009928:Organ Specificity; D015398:Signal Transduction; D013154:Spleen / Q000033:anatomy & histology; D014183:Transplantation, Heterologous
D008934:Mitogens; D004247:DNA