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

Liu, He; He, Zhaoyue; April, Simon Leonhard; Trefny, Marcel Philipp; Rougier, Jean-Sébastien; Salemi, Souzan; Olariu, Radu; Widmer, Hans Rudolf; Simon, Hans-Uwe (2019). Biochemical re-programming of human dermal stem cells to neurons by increasing mitochondrial membrane potential. Cell death and differentiation, 26(6), pp. 1048-1061. Nature Publishing Group 10.1038/s41418-018-0182-8

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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 (ψ). 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 ψ, 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 ψ-high subpopulation which produced more mitochondrial reactive oxygen species (ROS) and showed an enhanced neuronal differentiation capacity as compared to the ψ-low subpopulation. These data suggest that the ψ-low stem cells may function as the dormant stem cell population to sustain future neuronal differentiation by avoiding excessive ROS production. Thus, chemical modulation of PI3K activity, switching the metabotype of hDSCs to neurons, may have potential as an autologous transplantation strategy for neurodegenerative diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Neurochirurgie
09 Interdisciplinary Units > Microscopy Imaging Center MIC

UniBE Contributor:

Liu, He; He, Zhaoyue; April, Simon; Trefny, Marcel Philipp; Rougier, Jean-Sébastien; Salemi, Souzan; Olariu, Radu; Widmer, Hans Rudolf and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1350-9047

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Veronika Picha

Date Deposited:

04 Sep 2018 12:33

Last Modified:

12 May 2019 01:30

Publisher DOI:

10.1038/s41418-018-0182-8

PubMed ID:

30154448

URI:

https://boris.unibe.ch/id/eprint/119779

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