Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes

Abstract MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains la...

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Autores principales:	Sureni V. Mullegama, Steven D. Klein, Stephen R. Williams, Jeffrey W. Innis, Frank J. Probst, Chad Haldeman-Englert, Julian A. Martinez-Agosto, Ying Yang, Yuchen Tian, Sarah H. Elsea, Toshihiko Ezashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e6d18d28ad8c4705b934f15392ca5b20
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spelling	oai:doaj.org-article:e6d18d28ad8c4705b934f15392ca5b202021-12-02T14:49:17ZTranscriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes10.1038/s41598-021-90798-z2045-2322https://doaj.org/article/e6d18d28ad8c4705b934f15392ca5b202021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90798-zhttps://doaj.org/toc/2045-2322Abstract MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.Sureni V. MullegamaSteven D. KleinStephen R. WilliamsJeffrey W. InnisFrank J. ProbstChad Haldeman-EnglertJulian A. Martinez-AgostoYing YangYuchen TianSarah H. ElseaToshihiko EzashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sureni V. Mullegama Steven D. Klein Stephen R. Williams Jeffrey W. Innis Frank J. Probst Chad Haldeman-Englert Julian A. Martinez-Agosto Ying Yang Yuchen Tian Sarah H. Elsea Toshihiko Ezashi Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
description	Abstract MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.
format	article
author	Sureni V. Mullegama Steven D. Klein Stephen R. Williams Jeffrey W. Innis Frank J. Probst Chad Haldeman-Englert Julian A. Martinez-Agosto Ying Yang Yuchen Tian Sarah H. Elsea Toshihiko Ezashi
author_facet	Sureni V. Mullegama Steven D. Klein Stephen R. Williams Jeffrey W. Innis Frank J. Probst Chad Haldeman-Englert Julian A. Martinez-Agosto Ying Yang Yuchen Tian Sarah H. Elsea Toshihiko Ezashi
author_sort	Sureni V. Mullegama
title	Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
title_short	Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
title_full	Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
title_fullStr	Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
title_full_unstemmed	Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
title_sort	transcriptome analysis of mbd5-associated neurodevelopmental disorder (mand) neural progenitor cells reveals dysregulation of autism-associated genes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e6d18d28ad8c4705b934f15392ca5b20
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Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes

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