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Engineering Adult Neurogenesis and Gliogenesis

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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00155

Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1 and Neurog2

  • 1Brain Institute, Federal University of Rio Grande do Norte, Brazil
  • 2Institute for Analysis and Scientific Computing, Vienna University of Technology, Austria
  • 3Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Brazil
  • 4Centro de Biociências, Federal University of Rio Grande do Norte, Brazil

Reprogramming of somatic cells into induced pluripotent stem cells (iPS) or directly into cells from a different lineage, including neurons, has revolutionized research in regenerative medicine in recent years. Mesenchymal stem cells are good candidates for lineage reprogramming and autologous transplantation, since they can be easily isolated from accessible sources in adult humans, such as bone marrow and dental tissues. Here, we demonstrate that expression of the transcription factors (TFs) SRY (sex determining region Y)-box 2 (Sox2), Mammalian achaete-scute homolog 1 (Ascl1) or Neurogenin 2 (Neurog2) is sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC) into induced neurons (iNs). Furthermore, the combination of Sox2/Ascl1 or Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs showing electrical properties of mature neurons and establishing synaptic contacts with co-culture primary neurons. Finally, we show evidence supporting the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2) may induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs, suggesting that neuronal fate is determined by a combination of signals involving the TFs used for reprogramming but also the internal state of the converted cell. Altogether, the data presented here contribute to the advancement of techniques aiming at obtaining specific neuronal phenotypes from lineage-converted human somatic cells to treat neurological disorders.

Keywords: induced neurons, Lineage reprogramming, human mesenchymal stem cells, Umbilical Cord, Proneural genes

Received: 23 Apr 2018; Accepted: 17 May 2018.

Edited by:

Christophe Heinrich, INSERM U1208 Institut Cellule Souche et Cerveau, France

Reviewed by:

Carol Schuurmans, Sunnybrook Health Science Centre, Canada
Zhiping P. Pang, Rutgers University, The State University of New Jersey, United States  

Copyright: © 2018 Araújo, Hilscher, Marques Coelho, Golbert, Cornelio, Batistuzzo de Medeiros, Leão and Costa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Marcos R. Costa, Federal University of Rio Grande do Norte, Brain Institute, Av. Nascimento de Castro 2155, Lagoa Nova, Natal, 59056-450, Brazil, mrcosta@neuro.ufrn.br