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Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage

Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marke...

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Autores principales: Mak, Sally K., Huang, Y. Anne, Iranmanesh, Shifteh, Vangipuram, Malini, Sundararajan, Ramya, Nguyen, Loan, Langston, J. William, Schüle, Birgitt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339118/
https://www.ncbi.nlm.nih.gov/pubmed/22567022
http://dx.doi.org/10.1155/2012/140427
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author Mak, Sally K.
Huang, Y. Anne
Iranmanesh, Shifteh
Vangipuram, Malini
Sundararajan, Ramya
Nguyen, Loan
Langston, J. William
Schüle, Birgitt
author_facet Mak, Sally K.
Huang, Y. Anne
Iranmanesh, Shifteh
Vangipuram, Malini
Sundararajan, Ramya
Nguyen, Loan
Langston, J. William
Schüle, Birgitt
author_sort Mak, Sally K.
collection PubMed
description Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson's disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.
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spelling pubmed-33391182012-05-07 Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage Mak, Sally K. Huang, Y. Anne Iranmanesh, Shifteh Vangipuram, Malini Sundararajan, Ramya Nguyen, Loan Langston, J. William Schüle, Birgitt Stem Cells Int Research Article Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson's disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage. Hindawi Publishing Corporation 2012 2012-04-10 /pmc/articles/PMC3339118/ /pubmed/22567022 http://dx.doi.org/10.1155/2012/140427 Text en Copyright © 2012 Sally K. Mak et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mak, Sally K.
Huang, Y. Anne
Iranmanesh, Shifteh
Vangipuram, Malini
Sundararajan, Ramya
Nguyen, Loan
Langston, J. William
Schüle, Birgitt
Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
title Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
title_full Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
title_fullStr Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
title_full_unstemmed Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
title_short Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
title_sort small molecules greatly improve conversion of human-induced pluripotent stem cells to the neuronal lineage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339118/
https://www.ncbi.nlm.nih.gov/pubmed/22567022
http://dx.doi.org/10.1155/2012/140427
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