Reduced CYFIP1 in human neural progenitors results in dysregulation of schizophrenia and epilepsy gene networks

Rebecca A. Nebel, Dejian Zhao, Erika Pedrosa, Jill Kirschen, Herbert M. Lachman, Deyou Zheng, Brett S. Abrahams

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Deletions encompassing the BP1-2 region at 15q11.2 increase schizophrenia and epilepsy risk, but only some carriers have either disorder. To investigate the role of CYFIP1, a gene within the region, we performed knockdown experiments in human neural progenitors derived from donors with 2 copies of each gene at the BP1-2 locus. RNA-seq and cellular assays determined that knockdown of CYFIP1 compromised cytoskeletal remodeling. FMRP targets and postsynaptic density genes, each implicated in schizophrenia, were significantly overrepresented among differentially expressed genes (DEGs). Schizophrenia and/or epilepsy genes, but not those associated with randomly selected disorders, were likewise significantly overrepresented. Mirroring the variable expressivity seen in deletion carriers, marked between-line differences were observed for dysregulation of disease genes. Finally, a subset of DEGs showed a striking similarity to known epilepsy genes and represents novel disease candidates. Results support a role for CYFIP1 in disease and demonstrate that disease-related biological signatures are apparent prior to neuronal differentiation.

Original languageEnglish (US)
Article number0148039
JournalPLoS One
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

epilepsy
Gene Regulatory Networks
Epilepsy
Schizophrenia
Genes
genes
Post-Synaptic Density
line differences
schizophrenia
gene regulatory networks
Assays
RNA
loci
assays

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Reduced CYFIP1 in human neural progenitors results in dysregulation of schizophrenia and epilepsy gene networks. / Nebel, Rebecca A.; Zhao, Dejian; Pedrosa, Erika; Kirschen, Jill; Lachman, Herbert M.; Zheng, Deyou; Abrahams, Brett S.

In: PLoS One, Vol. 11, No. 1, 0148039, 01.01.2016.

Research output: Contribution to journalArticle

Nebel, Rebecca A. ; Zhao, Dejian ; Pedrosa, Erika ; Kirschen, Jill ; Lachman, Herbert M. ; Zheng, Deyou ; Abrahams, Brett S. / Reduced CYFIP1 in human neural progenitors results in dysregulation of schizophrenia and epilepsy gene networks. In: PLoS One. 2016 ; Vol. 11, No. 1.
@article{7462d1eb430940b2bead25b07eaa81ae,
title = "Reduced CYFIP1 in human neural progenitors results in dysregulation of schizophrenia and epilepsy gene networks",
abstract = "Deletions encompassing the BP1-2 region at 15q11.2 increase schizophrenia and epilepsy risk, but only some carriers have either disorder. To investigate the role of CYFIP1, a gene within the region, we performed knockdown experiments in human neural progenitors derived from donors with 2 copies of each gene at the BP1-2 locus. RNA-seq and cellular assays determined that knockdown of CYFIP1 compromised cytoskeletal remodeling. FMRP targets and postsynaptic density genes, each implicated in schizophrenia, were significantly overrepresented among differentially expressed genes (DEGs). Schizophrenia and/or epilepsy genes, but not those associated with randomly selected disorders, were likewise significantly overrepresented. Mirroring the variable expressivity seen in deletion carriers, marked between-line differences were observed for dysregulation of disease genes. Finally, a subset of DEGs showed a striking similarity to known epilepsy genes and represents novel disease candidates. Results support a role for CYFIP1 in disease and demonstrate that disease-related biological signatures are apparent prior to neuronal differentiation.",
author = "Nebel, {Rebecca A.} and Dejian Zhao and Erika Pedrosa and Jill Kirschen and Lachman, {Herbert M.} and Deyou Zheng and Abrahams, {Brett S.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0148039",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Reduced CYFIP1 in human neural progenitors results in dysregulation of schizophrenia and epilepsy gene networks

AU - Nebel, Rebecca A.

AU - Zhao, Dejian

AU - Pedrosa, Erika

AU - Kirschen, Jill

AU - Lachman, Herbert M.

AU - Zheng, Deyou

AU - Abrahams, Brett S.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Deletions encompassing the BP1-2 region at 15q11.2 increase schizophrenia and epilepsy risk, but only some carriers have either disorder. To investigate the role of CYFIP1, a gene within the region, we performed knockdown experiments in human neural progenitors derived from donors with 2 copies of each gene at the BP1-2 locus. RNA-seq and cellular assays determined that knockdown of CYFIP1 compromised cytoskeletal remodeling. FMRP targets and postsynaptic density genes, each implicated in schizophrenia, were significantly overrepresented among differentially expressed genes (DEGs). Schizophrenia and/or epilepsy genes, but not those associated with randomly selected disorders, were likewise significantly overrepresented. Mirroring the variable expressivity seen in deletion carriers, marked between-line differences were observed for dysregulation of disease genes. Finally, a subset of DEGs showed a striking similarity to known epilepsy genes and represents novel disease candidates. Results support a role for CYFIP1 in disease and demonstrate that disease-related biological signatures are apparent prior to neuronal differentiation.

AB - Deletions encompassing the BP1-2 region at 15q11.2 increase schizophrenia and epilepsy risk, but only some carriers have either disorder. To investigate the role of CYFIP1, a gene within the region, we performed knockdown experiments in human neural progenitors derived from donors with 2 copies of each gene at the BP1-2 locus. RNA-seq and cellular assays determined that knockdown of CYFIP1 compromised cytoskeletal remodeling. FMRP targets and postsynaptic density genes, each implicated in schizophrenia, were significantly overrepresented among differentially expressed genes (DEGs). Schizophrenia and/or epilepsy genes, but not those associated with randomly selected disorders, were likewise significantly overrepresented. Mirroring the variable expressivity seen in deletion carriers, marked between-line differences were observed for dysregulation of disease genes. Finally, a subset of DEGs showed a striking similarity to known epilepsy genes and represents novel disease candidates. Results support a role for CYFIP1 in disease and demonstrate that disease-related biological signatures are apparent prior to neuronal differentiation.

UR - http://www.scopus.com/inward/record.url?scp=84958212527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958212527&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0148039

DO - 10.1371/journal.pone.0148039

M3 - Article

C2 - 26824476

AN - SCOPUS:84958212527

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - 0148039

ER -