Conversion potential of marrow cells into lung cells fluctuates with cytokine-induced cell cycle.
Green fluorescent protein (GFP)-labeled marrow cells transplanted into lethally irradiated mice can be detected in the lungs of transplanted mice and have been shown to express lung-specific proteins while lacking the expression of hematopoietic markers. We have studied marrow cells induced to transit the cell cycle by exposure to interleukin-3 (IL-3), IL-6, IL-11, and Steel factor at different times of culture corresponding to different phases of cell cycle. We have found that marrow cells at the G(1)/S interface of the cell cycle have a three-fold increase in cells that assume a nonhematopoietic or pulmonary epithelial cell phenotype and that this increase is no longer seen in late S/G(2). These cells have been characterized as GFP(+) CD45(-) and GFP(+) cytokeratin(+). Thus, marrow cells with the capacity to convert into cells with a lung phenotype after transplantation show a reversible increase with cytokine-induced cell cycle transit. Previous studies have shown that the phenotype of bone marrow stem cells fluctuates reversibly as these cells traverse the cell cycle, leading to a continuum model of stem cell regulation. The present study indicates that marrow stem cell production of nonhematopoietic cells also fluctuates on a continuum.
Dooner
Mark S
MS
Department of Medical Oncology Research, Center for Stem Cell Biology Research, Rhode Island Hospital, Providence, RI 02903, USA. mdooner@lifespan.org
Aliotta
Jason M
JM
Pimentel
Jeffrey
J
Dooner
Gerri J
GJ
Abedi
Mehrdad
M
Colvin
Gerald
G
Liu
Qin
Q
Weier
Heinz-Ulli
HU
Johnson
Kevin W
KW
Quesenberry
Peter J
PJ
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002459:Cell Fusion; D002465:Cell Movement; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D000950:Antigens, Ly; D016207:Cytokines; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse