TY - JOUR AU - Barrell, William B. AU - Griffin, John N. AU - Harvey, Jessica-Lily AU - , HipSci Consortium AU - Danovi, Davide AU - Beales, Philip AU - Grigoriadis, Agamemnon E. AU - Liu, Karen J. AU - Durbin, Richard AU - Gaffney, Daniel AU - Agu, Chukwuma AU - Alderton, Alex AU - Amatya, Shrada AU - Danecek, Petr AU - Denton, Rachel AU - Goncalves, Angela AU - Halai, Reena AU - Harper, Sarah AU - Kirton, Chris AU - Knights, Andrew AU - Kolb-Kokocinski, Anja AU - Leha, Andreas AU - McCarthy, Shane AU - Memari, Yasin AU - Patel, Minal AU - Birney, Ewan AU - Stegle, Oliver AU - Paolo Casale, Francesco AU - Clarke, Laura AU - Harrison, Peter AU - Kilpinen, Helena AU - McCarthy, Davis AU - Streeter, Ian AU - Watt, Fiona AU - Denovi, Davide AU - Meleckyte, Ruta AU - Moens, Natalie AU - Ouwehand, Willem AU - Vallier, Ludovic AU - Lamond, Angus AU - Bensaddek, Dalila AU - Beales, Philip PY - 2019 M3 - Original Research TI - Induction of Neural Crest Stem Cells From Bardet–Biedl Syndrome Patient Derived hiPSCs JO - Frontiers in Molecular Neuroscience UR - https://www.frontiersin.org/articles/10.3389/fnmol.2019.00139 VL - 12 SN - 1662-5099 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 humans 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 modeling 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 characterize 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 toward a neural crest fate, which was also characterized 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 toward precision medicine approaches. ER -