Intrinsic Hematopoietic Stem Cell/Progenitor Plasticity: Inversions

Gerald A. Colvin, Jean François Lambert, Brian E. Moore, Jane E. Carlson, Mark S. Dooner, Mehrdad Abedi, Jan Cerny, Peter J. Quesenberry

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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 negativerhodaminelowHoechstlow 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.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalJournal of Cellular Physiology
Issue number1
StatePublished - Apr 2004
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology


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