Biochemical re-programming of human dermal stem cells to neurons by increasing mitochondrial membrane potential

Cell Death and Differentiation
He LiuHans-Uwe Simon

Abstract

Stem cells are generally believed to contain a small number of mitochondria, thus accounting for their glycolytic phenotype. We demonstrate here, however, that despite an indispensable glucose dependency, human dermal stem cells (hDSCs) contain very numerous mitochondria. Interestingly, these stem cells segregate into two distinct subpopulations. One exhibits high, the other low-mitochondrial membrane potentials (Δψm). We have made the same observations with mouse neural stem cells (mNSCs) which serve here as a complementary model to hDSCs. Strikingly, pharmacologic inhibition of phosphoinositide 3-kinase (PI3K) increased the overall Δψm, decreased the dependency on glycolysis and led to formation of TUJ1 positive, electrophysiologically functional neuron-like cells in both mNSCs and hDSCs, even in the absence of any neuronal growth factors. Furthermore, of the two, it was the Δψm-high subpopulation which produced more mitochondrial reactive oxygen species (ROS) and showed an enhanced neuronal differentiation capacity as compared to the Δψm-low subpopulation. These data suggest that the Δψm-low stem cells may function as the dormant stem cell population to sustain future neuronal differentiation by avoiding excessive ROS produc...Continue Reading

References

Sep 5, 2001·Nature Cell Biology·J G TomaF D Miller
Apr 11, 2006·Molecular Cell·Dos D SarbassovDavid M Sabatini
Oct 10, 2006·Development, Growth & Differentiation·Zegui LiLing Wei
Feb 7, 2007·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Karl J L FernandesFreda D Miller
Nov 1, 2007·Journal of Cell Science·Joao M Facucho-OliveiraJustin C St John
Nov 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ralph J DeBerardinisCraig B Thompson
Dec 8, 2007·The Journal of Biological Chemistry·Daniel F BogenhagenStephanie Burke
Aug 21, 2008·The Journal of Biological Chemistry·Stefan M SchiekeToren Finkel
Mar 7, 1927·The Journal of General Physiology·O WarburgE Negelein
Dec 17, 2009·Trends in Cell Biology·Andrew F MacAskill, Josef T Kittler
Jan 19, 2011·The Journal of Experimental Medicine·Amparo WolfAbhijit Guha
Aug 20, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Sarah K SteinbachMansoor Husain
Dec 21, 2011·Cell Research·Souzan SalemiHans-Uwe Simon
Apr 12, 2012·The Journal of Biological Chemistry·So-young JangEun Seong Hwang
May 1, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jessica LundqvistAnna Forsby
Aug 21, 2012·Biochimica Et Biophysica Acta·Pascale Belenguer, Luca Pellegrini
Jul 9, 2013·Seminars in Cancer Biology·He LiuHans-Uwe Simon
Oct 1, 2013·FEBS Letters·Wangyang XuZhugang Wang
Oct 15, 2013·Biochimica Et Biophysica Acta·A R EstevesS M Cardoso
Nov 28, 2013·The Journal of Experimental Medicine·Johannes Vom BergBurkhard Becher
Jul 20, 2014·Neuroscience Letters·Yu KamishibaharaNorio Shimizu
Jul 3, 2015·Stem Cells and Development·Anaïs WanetPatricia Renard
Feb 13, 2016·Seminars in Cell & Developmental Biology·Clifford D L Folmes, Andre Terzic
Oct 13, 2016·Nature Communications·Nicola VanniniMatthias P Lutolf

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
PCR
RNAseq
FACS
confocal microscopy
FCS
light microscopy
Protein Assay
Assay

Software Mentioned

ImageJ

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.