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

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 trans...

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Principais autores: Araújo, Jessica Alves de Medeiros, Hilscher, Markus M., Marques-Coelho, Diego, Golbert, Daiane C. F., Cornelio, Deborah A., Medeiros, Silvia R. Batistuzzo de, Leão, Richardson Naves, Costa, Marcos Romualdo
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Idioma:eng
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Assuntos:
induced neurons
lineage reprogramming
human mesenchymal stem cells
umbilical cord
proneural genes
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/25457
https://doi.org/10.3389/fncel.2018.00155
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spelling ri-123456789-254572021-07-09T21:19:11Z Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2 Araújo, Jessica Alves de Medeiros Hilscher, Markus M. Marques-Coelho, Diego Golbert, Daiane C. F. Cornelio, Deborah A. Medeiros, Silvia R. Batistuzzo de Leão, Richardson Naves Costa, Marcos Romualdo induced neurons lineage reprogramming human mesenchymal stem cells umbilical cord proneural genes 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. 2018-06-19T12:55:19Z 2018-06-19T12:55:19Z 2018-06-08 article ARAÚJO J.A.M. et al. Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2. Front. Cell. Neurosci., v. 12, n.155, jun./2018. https://repositorio.ufrn.br/jspui/handle/123456789/25457 https://doi.org/10.3389/fncel.2018.00155 eng Acesso Aberto application/pdf
institution Repositório Institucional
collection RI - UFRN
language eng
topic induced neurons
lineage reprogramming
human mesenchymal stem cells
umbilical cord
proneural genes
spellingShingle induced neurons
lineage reprogramming
human mesenchymal stem cells
umbilical cord
proneural genes
Araújo, Jessica Alves de Medeiros
Hilscher, Markus M.
Marques-Coelho, Diego
Golbert, Daiane C. F.
Cornelio, Deborah A.
Medeiros, Silvia R. Batistuzzo de
Leão, Richardson Naves
Costa, Marcos Romualdo
Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
description 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.
format article
author Araújo, Jessica Alves de Medeiros
Hilscher, Markus M.
Marques-Coelho, Diego
Golbert, Daiane C. F.
Cornelio, Deborah A.
Medeiros, Silvia R. Batistuzzo de
Leão, Richardson Naves
Costa, Marcos Romualdo
author_facet Araújo, Jessica Alves de Medeiros
Hilscher, Markus M.
Marques-Coelho, Diego
Golbert, Daiane C. F.
Cornelio, Deborah A.
Medeiros, Silvia R. Batistuzzo de
Leão, Richardson Naves
Costa, Marcos Romualdo
author_sort Araújo, Jessica Alves de Medeiros
title Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
title_short Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
title_full Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
title_fullStr Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
title_full_unstemmed Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
title_sort direct reprogramming of adult human somatic stem cells into functional neurons using sox2, ascl1, and neurog2
publishDate 2018
url https://repositorio.ufrn.br/jspui/handle/123456789/25457
https://doi.org/10.3389/fncel.2018.00155
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