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

Detalhes bibliográficos
Autor(a) principal: Araújo, Jessica Alves de Medeiros
Data de Publicação: 2018
Outros Autores: Hilscher, Markus M., Marques-Coelho, Diego, Golbert, Daiane C. F., Cornelio, Deborah A., Medeiros, Silvia R. Batistuzzo de, Leão, Richardson Naves, Costa, Marcos Romualdo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRN
Texto Completo: https://repositorio.ufrn.br/jspui/handle/123456789/25457
https://doi.org/10.3389/fncel.2018.00155
Resumo: 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.
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spelling Araújo, Jessica Alves de MedeirosHilscher, Markus M.Marques-Coelho, DiegoGolbert, Daiane C. F.Cornelio, Deborah A.Medeiros, Silvia R. Batistuzzo deLeão, Richardson NavesCosta, Marcos Romualdo2018-06-19T12:55:19Z2018-06-19T12:55:19Z2018-06-08ARAÚJO 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/123456789/25457https://doi.org/10.3389/fncel.2018.00155enginduced neuronslineage reprogramminghuman mesenchymal stem cellsumbilical cordproneural genesDirect reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleReprogramming 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALMarcosCosta_ICe_Direct Reprogramming_2018.pdfMarcosCosta_ICe_Direct Reprogramming_2018.pdfMarcosCosta_ICe_Direct reprogramming_2018application/pdf3754022https://repositorio.ufrn.br/bitstream/123456789/25457/1/MarcosCosta_ICe_Direct%20Reprogramming_2018.pdfc66fd19369c9441e6d6bd78418e060d0MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.ufrn.br/bitstream/123456789/25457/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52TEXTMarcosCosta_ICe_Direct Reprogramming_2018.pdf.txtMarcosCosta_ICe_Direct Reprogramming_2018.pdf.txtExtracted texttext/plain66472https://repositorio.ufrn.br/bitstream/123456789/25457/3/MarcosCosta_ICe_Direct%20Reprogramming_2018.pdf.txt1cbab9bc8a2fd91310d91beffcea33e0MD53THUMBNAILMarcosCosta_ICe_Direct Reprogramming_2018.pdf.jpgMarcosCosta_ICe_Direct Reprogramming_2018.pdf.jpgIM Thumbnailimage/jpeg11467https://repositorio.ufrn.br/bitstream/123456789/25457/4/MarcosCosta_ICe_Direct%20Reprogramming_2018.pdf.jpga8decfb210b6649040340e734e5a81dfMD54123456789/254572021-07-09 18:19:11.9oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-07-09T21:19:11Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.pt_BR.fl_str_mv Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
title Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
spellingShingle Direct reprogramming of adult human somatic stem cells into functional neurons using Sox2, Ascl1, and Neurog2
Araújo, Jessica Alves de Medeiros
induced neurons
lineage reprogramming
human mesenchymal stem cells
umbilical cord
proneural genes
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
author Araújo, Jessica Alves de Medeiros
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_role author
author2 Hilscher, Markus M.
Marques-Coelho, Diego
Golbert, Daiane C. F.
Cornelio, Deborah A.
Medeiros, Silvia R. Batistuzzo de
Leão, Richardson Naves
Costa, Marcos Romualdo
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv 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
dc.subject.por.fl_str_mv induced neurons
lineage reprogramming
human mesenchymal stem cells
umbilical cord
proneural genes
topic induced neurons
lineage reprogramming
human mesenchymal stem cells
umbilical cord
proneural genes
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.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-06-19T12:55:19Z
dc.date.available.fl_str_mv 2018-06-19T12:55:19Z
dc.date.issued.fl_str_mv 2018-06-08
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://repositorio.ufrn.br/jspui/handle/123456789/25457
dc.identifier.doi.none.fl_str_mv https://doi.org/10.3389/fncel.2018.00155
identifier_str_mv 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.
url https://repositorio.ufrn.br/jspui/handle/123456789/25457
https://doi.org/10.3389/fncel.2018.00155
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