Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain
Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ect...
Main Authors: | , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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SAGE Publishing
2021-01-01
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Series: | Cell Transplantation |
Online Access: | https://doi.org/10.1177/0963689720978219 |
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author | Andrea Tenorio-Mina Daniel Cortés Joel Esquivel-Estudillo Adolfo López-Ornelas Alejandro Cabrera-Wrooman Rolando Lara-Rodarte Itzel Escobedo-Avila Fernanda Vargas-Romero Diana Toledo-Hernández Enrique Estudillo Juan José Acevedo-Fernández Jesús Santa-Olalla Tapia Iván Velasco |
author_facet | Andrea Tenorio-Mina Daniel Cortés Joel Esquivel-Estudillo Adolfo López-Ornelas Alejandro Cabrera-Wrooman Rolando Lara-Rodarte Itzel Escobedo-Avila Fernanda Vargas-Romero Diana Toledo-Hernández Enrique Estudillo Juan José Acevedo-Fernández Jesús Santa-Olalla Tapia Iván Velasco |
author_sort | Andrea Tenorio-Mina |
collection | DOAJ |
description | Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations. |
first_indexed | 2024-12-21T12:48:31Z |
format | Article |
id | doaj.art-5a21c2b0c73548b58e451802d51f744b |
institution | Directory Open Access Journal |
issn | 1555-3892 |
language | English |
last_indexed | 2024-12-21T12:48:31Z |
publishDate | 2021-01-01 |
publisher | SAGE Publishing |
record_format | Article |
series | Cell Transplantation |
spelling | doaj.art-5a21c2b0c73548b58e451802d51f744b2022-12-21T19:03:33ZengSAGE PublishingCell Transplantation1555-38922021-01-013010.1177/0963689720978219Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat BrainAndrea Tenorio-Mina0Daniel Cortés1Joel Esquivel-Estudillo2Adolfo López-Ornelas3Alejandro Cabrera-Wrooman4Rolando Lara-Rodarte5Itzel Escobedo-Avila6Fernanda Vargas-Romero7Diana Toledo-Hernández8Enrique Estudillo9Juan José Acevedo-Fernández10Jesús Santa-Olalla Tapia11Iván Velasco12 Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico Unidad de Diagnóstico y Medicina Molecular, “Dr. Ruy Pérez Tamayo”, Hospital del Niño Morelense/Facultad de Medicina-UAEM, Zapata, Morelos, Mexico División de Investigación, Hospital Juárez de México, Mexico City, Mexico Instituto Nacional de Rehabilitación, Mexico City, Mexico Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico Centro de Investigación en Dinámica Celular, Instituto de Ciencias, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico Unidad de Diagnóstico y Medicina Molecular, “Dr. Ruy Pérez Tamayo”, Hospital del Niño Morelense/Facultad de Medicina-UAEM, Zapata, Morelos, Mexico Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, MexicoHuman skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.https://doi.org/10.1177/0963689720978219 |
spellingShingle | Andrea Tenorio-Mina Daniel Cortés Joel Esquivel-Estudillo Adolfo López-Ornelas Alejandro Cabrera-Wrooman Rolando Lara-Rodarte Itzel Escobedo-Avila Fernanda Vargas-Romero Diana Toledo-Hernández Enrique Estudillo Juan José Acevedo-Fernández Jesús Santa-Olalla Tapia Iván Velasco Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain Cell Transplantation |
title | Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain |
title_full | Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain |
title_fullStr | Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain |
title_full_unstemmed | Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain |
title_short | Human Keratinocytes Adopt Neuronal Fates After Transplantation in the Developing Rat Brain |
title_sort | human keratinocytes adopt neuronal fates after transplantation in the developing rat brain |
url | https://doi.org/10.1177/0963689720978219 |
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