The chiaroscuro stem cell: a unified stem cell theory

• Published in: Blood Vol. 100; no. 13; pp. 4266 - 4271
• Main Authors: Quesenberry, Peter J., Colvin, Gerald A., Lambert, Jean-Francois
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.12.2002; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cats; Cell Cycle; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell Division; Cell physiology; Cells, Cultured - drug effects; Chromatin - physiology; Cytokines - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Graft Survival; Hematopoiesis - drug effects; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic System - embryology; Hematopoietic System - growth & development; Humans; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Models, Biological; Molecular and cellular biology; Receptors, Cell Surface - physiology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Hematopoiesis; Theory; Stem cell; Cell biology; Hematopoietic cell; Hypothesis; Cell origin
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-04-1246

Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraftable stem cell may be partially masked in nonsynchronized marrow cell populations. A general model indicates a marrow cell that can continually change its surface receptor expression and thus responds to external stimuli differently at different points in the cell cycle.