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Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs

Research output: Contribution to journalArticle

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Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs. / Barrell, William Barclay; Griffin, John Noel; Harvey, Jessica-Lily; HipSci Consortium, ; Danovi, Davide; Beales, Philip; Grigoriadis, Agamemnon; Liu, Karen Jasmine.

In: Frontiers in Molecular Neuroscience, Vol. 12, 139, 21.06.2019.

Research output: Contribution to journalArticle

Harvard

Barrell, WB, Griffin, JN, Harvey, J-L, HipSci Consortium, , Danovi, D, Beales, P, Grigoriadis, A & Liu, KJ 2019, 'Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs', Frontiers in Molecular Neuroscience, vol. 12, 139. https://doi.org/10.3389/fnmol.2019.00139

APA

Barrell, W. B., Griffin, J. N., Harvey, J-L., HipSci Consortium, Danovi, D., Beales, P., ... Liu, K. J. (2019). Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs. Frontiers in Molecular Neuroscience, 12, [139]. https://doi.org/10.3389/fnmol.2019.00139

Vancouver

Barrell WB, Griffin JN, Harvey J-L, HipSci Consortium , Danovi D, Beales P et al. Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs. Frontiers in Molecular Neuroscience. 2019 Jun 21;12. 139. https://doi.org/10.3389/fnmol.2019.00139

Author

Barrell, William Barclay ; Griffin, John Noel ; Harvey, Jessica-Lily ; HipSci Consortium, ; Danovi, Davide ; Beales, Philip ; Grigoriadis, Agamemnon ; Liu, Karen Jasmine. / Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs. In: Frontiers in Molecular Neuroscience. 2019 ; Vol. 12.

Bibtex Download

@article{91995ccc87094ad084acee8708347477,
title = "Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs",
abstract = "Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in human due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage. Thus, a unique opportunity is offered for modelling neurocristopathies using patient specific stem cell lines. In this work, we make use of hiPSCs derived from patients affected by the Bardet-Biedl Syndrome (BBS) ciliopathy. BBS patients often exhibit subclinical craniofacial dysmorphisms that are likely to be associated with the neural crest-derived facial skeleton. We focus on hiPSCs carrying variants in the BBS10 gene, which encodes a protein forming part of a chaperonin-like complex associated with the cilium. Here, we establish a pipeline for profiling hiPSCs during differentiation toward the neural crest stem cell fate. This can be used to characterise the differentiation properties of the neural crest-like cells. Two different BBS10 mutant lines showed a reduction in expression of the characteristic neural crest gene expression profile. Further analysis of both BBS10 mutant lines highlighted the inability of these mutant lines to differentiate towards a neural crest fate, which was also characterised by a decreased WNT and BMP response. Altogether, our study suggests a requirement for wild-type BBS10 in human neural crest development. In the long term, approaches such as the one we describe will allow direct comparison of disease-specific cell lines. This will provide valuable insights into the relationships between genetic background and heterogeneity in cellular models. The possibility of integrating laboratory data with clinical phenotypes will move us towards precision medicine approaches.",
keywords = "BBS, Bardet–Biedl Syndrome, HiPSCs, Human induced pluripotent stem cells, Neural crest",
author = "Barrell, {William Barclay} and Griffin, {John Noel} and Jessica-Lily Harvey and {HipSci Consortium} and Davide Danovi and Philip Beales and Agamemnon Grigoriadis and Liu, {Karen Jasmine}",
year = "2019",
month = "6",
day = "21",
doi = "10.3389/fnmol.2019.00139",
language = "English",
volume = "12",
journal = "Frontiers in Molecular Neuroscience",
issn = "1662-5099",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Induction of neural crest stem cells from Bardet-Biedl Syndrome patient derived hiPSCs

AU - Barrell, William Barclay

AU - Griffin, John Noel

AU - Harvey, Jessica-Lily

AU - HipSci Consortium, null

AU - Danovi, Davide

AU - Beales, Philip

AU - Grigoriadis, Agamemnon

AU - Liu, Karen Jasmine

PY - 2019/6/21

Y1 - 2019/6/21

N2 - Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in human due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage. Thus, a unique opportunity is offered for modelling neurocristopathies using patient specific stem cell lines. In this work, we make use of hiPSCs derived from patients affected by the Bardet-Biedl Syndrome (BBS) ciliopathy. BBS patients often exhibit subclinical craniofacial dysmorphisms that are likely to be associated with the neural crest-derived facial skeleton. We focus on hiPSCs carrying variants in the BBS10 gene, which encodes a protein forming part of a chaperonin-like complex associated with the cilium. Here, we establish a pipeline for profiling hiPSCs during differentiation toward the neural crest stem cell fate. This can be used to characterise the differentiation properties of the neural crest-like cells. Two different BBS10 mutant lines showed a reduction in expression of the characteristic neural crest gene expression profile. Further analysis of both BBS10 mutant lines highlighted the inability of these mutant lines to differentiate towards a neural crest fate, which was also characterised by a decreased WNT and BMP response. Altogether, our study suggests a requirement for wild-type BBS10 in human neural crest development. In the long term, approaches such as the one we describe will allow direct comparison of disease-specific cell lines. This will provide valuable insights into the relationships between genetic background and heterogeneity in cellular models. The possibility of integrating laboratory data with clinical phenotypes will move us towards precision medicine approaches.

AB - Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in human due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage. Thus, a unique opportunity is offered for modelling neurocristopathies using patient specific stem cell lines. In this work, we make use of hiPSCs derived from patients affected by the Bardet-Biedl Syndrome (BBS) ciliopathy. BBS patients often exhibit subclinical craniofacial dysmorphisms that are likely to be associated with the neural crest-derived facial skeleton. We focus on hiPSCs carrying variants in the BBS10 gene, which encodes a protein forming part of a chaperonin-like complex associated with the cilium. Here, we establish a pipeline for profiling hiPSCs during differentiation toward the neural crest stem cell fate. This can be used to characterise the differentiation properties of the neural crest-like cells. Two different BBS10 mutant lines showed a reduction in expression of the characteristic neural crest gene expression profile. Further analysis of both BBS10 mutant lines highlighted the inability of these mutant lines to differentiate towards a neural crest fate, which was also characterised by a decreased WNT and BMP response. Altogether, our study suggests a requirement for wild-type BBS10 in human neural crest development. In the long term, approaches such as the one we describe will allow direct comparison of disease-specific cell lines. This will provide valuable insights into the relationships between genetic background and heterogeneity in cellular models. The possibility of integrating laboratory data with clinical phenotypes will move us towards precision medicine approaches.

KW - BBS

KW - Bardet–Biedl Syndrome

KW - HiPSCs

KW - Human induced pluripotent stem cells

KW - Neural crest

UR - http://www.scopus.com/inward/record.url?scp=85068445894&partnerID=8YFLogxK

U2 - 10.3389/fnmol.2019.00139

DO - 10.3389/fnmol.2019.00139

M3 - Article

VL - 12

JO - Frontiers in Molecular Neuroscience

JF - Frontiers in Molecular Neuroscience

SN - 1662-5099

M1 - 139

ER -

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