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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Main Authors: Sally K. Mak, Y. Anne Huang, Shifteh Iranmanesh, Malini Vangipuram, Ramya Sundararajan, Loan Nguyen, J. William Langston, Birgitt Schüle
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2012/140427
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author Sally K. Mak
Y. Anne Huang
Shifteh Iranmanesh
Malini Vangipuram
Ramya Sundararajan
Loan Nguyen
J. William Langston
Birgitt Schüle
author_facet Sally K. Mak
Y. Anne Huang
Shifteh Iranmanesh
Malini Vangipuram
Ramya Sundararajan
Loan Nguyen
J. William Langston
Birgitt Schüle
author_sort Sally K. Mak
collection DOAJ
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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issn 1687-966X
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publishDate 2012-01-01
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series Stem Cells International
spelling doaj-art-27d029443e384e9a9aa730c624be3d062025-02-03T05:51:03ZengWileyStem Cells International1687-966X1687-96782012-01-01201210.1155/2012/140427140427Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal LineageSally K. Mak0Y. Anne Huang1Shifteh Iranmanesh2Malini Vangipuram3Ramya Sundararajan4Loan Nguyen5J. William Langston6Birgitt Schüle7Basic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USABasic Research Department, The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA 94085, USAEfficient 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.http://dx.doi.org/10.1155/2012/140427
spellingShingle Sally K. Mak
Y. Anne Huang
Shifteh Iranmanesh
Malini Vangipuram
Ramya Sundararajan
Loan Nguyen
J. William Langston
Birgitt Schüle
Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage
Stem Cells International
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
url http://dx.doi.org/10.1155/2012/140427
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