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. 2008;1(1):2-21.
Epub 2008 Jan 20.

Stem cells, phenotypic inversion, and differentiation

Robert W Siggins, Ping Zhang, David Welsh, Nicole J Lecapitaine, Steve Nelson

Stem cells, phenotypic inversion, and differentiation

Robert W Siggins et al. Int J Clin Exp Med. 2008.

Abstract

Stem cells possess the potential to cure a myriad of ailments ranging from congenital diseases to illnesses acquired through the physiological process of aging. In the adult, these cells are extremely rare and often difficult to isolate in numbers sufficient to apply to medical treatment. Ex vivo expansion of these cells will be required for most meaningful interventions. The discovery of stem/progenitor cell inversion offers a new avenue for obtaining sufficient numbers of stem cells. Adult progenitor cells are much more common than quiescent stem cells and can be isolated with minimal interventions; therefore, inversion of progenitors to stem cells may become a feasible approach for therapeutic purposes. Stem cells are known to possess few mitochondria, and mitochondrial biogenesis is required for stem cell differentiation. The microtubule cytoskeleton is a major regulator for mitochondrial biogenesis. Investigations in the area of controlling cell differentiation and inducing phenotypic inversion, possibly through manipulation of mitochondrial biogenesis, may contribute to stem cell-based therapies.

Keywords: Stem cells; differentiation; inversion; microtubules; mitochondria.

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Figures

Figure 1
Figure 1
Murine Stem/Progenitor Cell Inversion in the Niche. (1) CD38+ stem cell attached to stromal cell in niche. (2) Stem cell undergoing asymmetric division. (3) CD38+ stem cell remains in the niche. (4) CD34+ progenitor cell receives signals from the microenvironment. (5) CD34+ progenitor cell may leave the niche and continue differentiating, or invert and remain in the niche as a new CD38+ stem cell.
Figure 2
Figure 2
Signal Transduction Pathway for Regulators of PGC-1α Expression and Mitochondrial Biogenesis. A) Regulators of PGC-1α are interconnected in a complex network of positive and negative feedback loops. This ensures that a prolonged signal favoring mitochondrial biogenesis is required for enlargement of the mitochondrial pool. B) Transcriptional control of PGC-1α expression and mitochondrial biogenesis.
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