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

Exp Cell Res. 2019 Oct 1;383(1):111469. doi: 10.1016/j.yexcr.2019.06.014. Epub 2019 Jul 12.


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.

Keywords: Autism spectrum disorder; Disease modeling; Induced pluripotent stem cell; Neural development; Neural stem cell; Neurexin; Neurexin-1 alpha; Single cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Alleles
  • Autistic Disorder / genetics
  • Autistic Disorder / pathology*
  • Calcium-Binding Proteins / genetics*
  • Cell Differentiation
  • Gene Deletion*
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology*
  • Nerve Tissue Proteins / genetics*
  • Neural Cell Adhesion Molecules / genetics*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology*
  • Neurogenesis / genetics
  • Single-Cell Analysis / methods*


  • Calcium-Binding Proteins
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules