AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
Over the recent years, the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain Containing 1) chromatin-associated factor has triggered increasing interest after the identification of variants in three rare and unrelated diseases, type 2 Facio Scapulo Humeral Dystrophy (FSHD2), Bosma A...
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doaj-a79f48bb80374f30b99138b221ba7b8e2021-07-23T13:31:34ZengMDPI AGBiomedicines2227-90592021-06-01975175110.3390/biomedicines9070751AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia SyndromeCamille Laberthonnière0Elva Maria Novoa-del-Toro1Raphaël Chevalier2Natacha Broucqsault3Vanitha Venkoba Rao4Jean Philippe Trani5Karine Nguyen6Shifeng Xue7Bruno Reversade8Jérôme D. Robin9Anais Baudot10Frédérique Magdinier11Aix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceDepartment of Biological Sciences, National University of Singapore, Singapore 117558, SingaporeAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceDepartment of Biological Sciences, National University of Singapore, Singapore 117558, SingaporeInstitute of Molecular and Cell Biology, A*STAR, Singapore 138632, SingaporeAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceAix-Marseille Univ-INSERM, MMG, 13005 Marseille, FranceOver the recent years, the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain Containing 1) chromatin-associated factor has triggered increasing interest after the identification of variants in three rare and unrelated diseases, type 2 Facio Scapulo Humeral Dystrophy (FSHD2), Bosma Arhinia and Microphthalmia Syndrome (BAMS), and the more recently isolated hypogonadotrophic hypogonadism (IHH) combined pituitary hormone deficiency (CPHD) and septo-optic dysplasia (SOD). However, it remains unclear why certain mutations lead to a specific muscle defect in FSHD while other are associated with severe congenital anomalies. To gain further insights into the specificity of SMCHD1 variants and identify pathways associated with the BAMS phenotype and related neural crest defects, we derived induced pluripotent stem cells from patients carrying a mutation in this gene. We differentiated these cells in neural crest stem cells and analyzed their transcriptome by RNA-Seq. Besides classical differential expression analyses, we analyzed our data using MOGAMUN, an algorithm allowing the extraction of active modules by integrating differential expression data with biological networks. We found that in BAMS neural crest cells, all subnetworks that are associated with differentially expressed genes converge toward a predominant role for AKT signaling in the control of the cell proliferation–migration balance. Our findings provide further insights into the distinct mechanism by which defects in neural crest migration might contribute to the craniofacial anomalies in BAMS.https://www.mdpi.com/2227-9059/9/7/751SMCHD1Bosma Arhinia and Microphthalmia SyndromeFacio Scapulo Humeral DystrophyRNA-Seqneural crest stem cellsinduced pluripotent stem cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Camille Laberthonnière Elva Maria Novoa-del-Toro Raphaël Chevalier Natacha Broucqsault Vanitha Venkoba Rao Jean Philippe Trani Karine Nguyen Shifeng Xue Bruno Reversade Jérôme D. Robin Anais Baudot Frédérique Magdinier |
spellingShingle |
Camille Laberthonnière Elva Maria Novoa-del-Toro Raphaël Chevalier Natacha Broucqsault Vanitha Venkoba Rao Jean Philippe Trani Karine Nguyen Shifeng Xue Bruno Reversade Jérôme D. Robin Anais Baudot Frédérique Magdinier AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome Biomedicines SMCHD1 Bosma Arhinia and Microphthalmia Syndrome Facio Scapulo Humeral Dystrophy RNA-Seq neural crest stem cells induced pluripotent stem cells |
author_facet |
Camille Laberthonnière Elva Maria Novoa-del-Toro Raphaël Chevalier Natacha Broucqsault Vanitha Venkoba Rao Jean Philippe Trani Karine Nguyen Shifeng Xue Bruno Reversade Jérôme D. Robin Anais Baudot Frédérique Magdinier |
author_sort |
Camille Laberthonnière |
title |
AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome |
title_short |
AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome |
title_full |
AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome |
title_fullStr |
AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome |
title_full_unstemmed |
AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome |
title_sort |
akt signaling modifies the balance between cell proliferation and migration in neural crest cells from patients affected with bosma arhinia and microphthalmia syndrome |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2021-06-01 |
description |
Over the recent years, the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain Containing 1) chromatin-associated factor has triggered increasing interest after the identification of variants in three rare and unrelated diseases, type 2 Facio Scapulo Humeral Dystrophy (FSHD2), Bosma Arhinia and Microphthalmia Syndrome (BAMS), and the more recently isolated hypogonadotrophic hypogonadism (IHH) combined pituitary hormone deficiency (CPHD) and septo-optic dysplasia (SOD). However, it remains unclear why certain mutations lead to a specific muscle defect in FSHD while other are associated with severe congenital anomalies. To gain further insights into the specificity of SMCHD1 variants and identify pathways associated with the BAMS phenotype and related neural crest defects, we derived induced pluripotent stem cells from patients carrying a mutation in this gene. We differentiated these cells in neural crest stem cells and analyzed their transcriptome by RNA-Seq. Besides classical differential expression analyses, we analyzed our data using MOGAMUN, an algorithm allowing the extraction of active modules by integrating differential expression data with biological networks. We found that in BAMS neural crest cells, all subnetworks that are associated with differentially expressed genes converge toward a predominant role for AKT signaling in the control of the cell proliferation–migration balance. Our findings provide further insights into the distinct mechanism by which defects in neural crest migration might contribute to the craniofacial anomalies in BAMS. |
topic |
SMCHD1 Bosma Arhinia and Microphthalmia Syndrome Facio Scapulo Humeral Dystrophy RNA-Seq neural crest stem cells induced pluripotent stem cells |
url |
https://www.mdpi.com/2227-9059/9/7/751 |
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