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Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality

Lam, Matti LU ; Moslem, Mohsen ; Bryois, Julien ; Pronk, Robin J ; Uhlin, Elias ; Ellström, Ivar Dehnisch ; Laan, Loora ; Olive, Jessica ; Morse, Rebecca and Rönnholm, Harriet , et al. (2019) In Experimental Cell Research 383(1).
Abstract

We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia. Furthermore, neuronal cells carrying NRXN1-alpha deletion were identified as immature by single cell RNA-seq analysis, displayed significant depression in... (More)

We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia. Furthermore, neuronal cells carrying NRXN1-alpha deletion were identified as immature by single cell RNA-seq analysis, displayed significant depression in calcium signaling activity and presented impaired maturation action potential profile in neurons investigated with electrophysiology. Our observations propose NRXN1-alpha plays an important role for the efficient establishment of neural stem cells, in neuronal differentiation and in maturation of functional excitatory neuronal cells.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Action Potentials, Alleles, Autistic Disorder/genetics, Calcium-Binding Proteins/genetics, Cell Differentiation, Gene Deletion, Humans, Induced Pluripotent Stem Cells/metabolism, Nerve Tissue Proteins/genetics, Neural Cell Adhesion Molecules/genetics, Neural Stem Cells/metabolism, Neurogenesis/genetics, Single-Cell Analysis/methods
in
Experimental Cell Research
volume
383
issue
1
article number
111469
pages
10 pages
publisher
Academic Press
external identifiers
  • scopus:85068909985
  • pmid:31302032
ISSN
1090-2422
DOI
10.1016/j.yexcr.2019.06.014
language
English
LU publication?
no
id
0e4a98bd-e5b4-4bd7-9bb4-bb569f52da54
date added to LUP
2021-08-09 15:39:39
date last changed
2024-05-18 12:22:31
@article{0e4a98bd-e5b4-4bd7-9bb4-bb569f52da54,
  abstract     = {{<p>We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia. Furthermore, neuronal cells carrying NRXN1-alpha deletion were identified as immature by single cell RNA-seq analysis, displayed significant depression in calcium signaling activity and presented impaired maturation action potential profile in neurons investigated with electrophysiology. Our observations propose NRXN1-alpha plays an important role for the efficient establishment of neural stem cells, in neuronal differentiation and in maturation of functional excitatory neuronal cells.</p>}},
  author       = {{Lam, Matti and Moslem, Mohsen and Bryois, Julien and Pronk, Robin J and Uhlin, Elias and Ellström, Ivar Dehnisch and Laan, Loora and Olive, Jessica and Morse, Rebecca and Rönnholm, Harriet and Louhivuori, Lauri and Korol, Sergiy V and Dahl, Niklas and Uhlén, Per and Anderlid, Britt-Marie and Kele, Malin and Sullivan, Patrick F and Falk, Anna}},
  issn         = {{1090-2422}},
  keywords     = {{Action Potentials; Alleles; Autistic Disorder/genetics; Calcium-Binding Proteins/genetics; Cell Differentiation; Gene Deletion; Humans; Induced Pluripotent Stem Cells/metabolism; Nerve Tissue Proteins/genetics; Neural Cell Adhesion Molecules/genetics; Neural Stem Cells/metabolism; Neurogenesis/genetics; Single-Cell Analysis/methods}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{Academic Press}},
  series       = {{Experimental Cell Research}},
  title        = {{Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality}},
  url          = {{https://lup.lub.lu.se/search/files/101034796/Single_cell_analysis_of_autism.pdf}},
  doi          = {{10.1016/j.yexcr.2019.06.014}},
  volume       = {{383}},
  year         = {{2019}},
}