Intrinsic hematopoietic stem cell/progenitor plasticity: Inversions.
Traditional concepts indicate that stem cells give rise to progenitor cells in a hierarchical system. We studied murine engraftable stem cells (ESCs) and progenitors in in vitro and found that ESC and progenitors exist in a reversible continuum, rather then a hierarchy. B6.SJL and BALB/c marrow cells were serially cultured with thrombopoietin (TPO), FLT-3 ligand (FLT-3L), and steel factor through cell cycle. Progenitors (high-proliferative potential colony-forming cells (HPP-CFC) and colony-forming unit culture (CFU-c)) and ESC capacity was determined. The cell cycle status of purified lineage(negative)rhodamine(low)Hoechst(low) stem cells was determined under the same conditions using tritiated thymidine incorporation and cell counts. We found an inverse relationship between progenitors and ESC, which occurred during the first cell cycle transit and was reversible. We have termed these progenitor/stem cell inversions and found that these inversions were consistently seen at 28-32 h of culture, representing early S-phase. We observed 13 major reversible increases in progenitor numbers from one time-point to another during the first cell cycle transit; this was coupled with 11 major ESC decreases and in 2 instances ESC were at baseline. These studies indicate that primitive marrow cells reversibly shift from ESC to progenitors without differentiation occurring. They exist as a fluctuating continuum.
Roger Williams Medical Center, Department of Research, Adele Decof Cancer Center, Providence, Rhode Island 02908-4735, USA. gcolvin@rwmc.org
Gerald A
GA
Colvin
Jean-François
JF
Lambert
Brian E
BE
Moore
Jane E
JE
Carlson
Mark S
MS
Dooner
Mehrdad
M
Abedi
Jan
J
Cerny
Peter J
PJ
Quesenberry
D000818:Animals; D015139:Blotting, Southern; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D016026:Bone Marrow Transplantation; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology
D008565:Membrane Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D013926:Thrombopoietin