Differentiation hotspots: The deterioration of hierarchy and stochasm

Gerald A. Colvin, Jean Francois Lambert, Mehrdad Abedi, Mark S. Dooner, Delia Demers, Brian E. Moore, Debbie Greer, Jason M. Aliotta, Jeff Pimentel, Jan Cerny, Lawrence G. Lum, Peter J. Quesenberry

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The conception of the present-day model of hematopoiesis was begun by the work of Professor Ernst Neumann in the 19th century when he established that immature blood cells in the bone marrow migrate out into the blood vessels. Here was the birth of the hierarchical model of hematopoiesis. Jumping 135 years into the present day, recent data suggests that the stem cell regulation is not based on the classic hierarchical model, but instead more on a functional continuum. Presumptively, chromatin remodeling with cycle transit underlies changes in gene expression. This implies that the differentiative potential of primitive stem cells should also shift with cycle transit. This model proposes a less rigid system, at least in the early stem cell and progenitor compartments in which the functional characteristics of stem cells change as they go through cycle transit. We have shown that hematopoietic stem cells reversibly shift their engraftment phenotype with cytokine induced cell cycle transit. Other shifts include adhesion protein expression, cytokine receptor expression, gene expression, and progenitor phenotype. We have also found differentiation "hotspots", culture times (reflective of cell cycle state) at which stem cell differentiation was directed toward a specific lineage. This data inaugurates the end of a pure stochastic model. This work complements existing scientific work without discounting it and adds an additional dimension of complexity (or simplicity) to the process of hematopoiesis.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalBlood Cells, Molecules, and Diseases
Issue number1
StatePublished - Jan 2004
Externally publishedYes


  • Bone marrow transplantation
  • Cell differentiation
  • Hematopoietic cell growth factors
  • Hematopoietic stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology


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