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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
- Source :
- Experimental Cell Research. 383:111469
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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 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.
- Subjects :
- 0301 basic medicine
Neurogenesis
Cellular differentiation
Induced Pluripotent Stem Cells
Neurexin
Action Potentials
Nerve Tissue Proteins
Biology
03 medical and health sciences
0302 clinical medicine
Neural Stem Cells
medicine
Humans
Autistic Disorder
Autism spectrum disorder
Single cell RNA sequencing
Progenitor cell
Induced pluripotent stem cell
Neural Cell Adhesion Molecules
Neurexin-1 alpha
Alleles
Calcium-Binding Proteins
Neurosciences
Cell Differentiation
Cell Biology
medicine.disease
Neural stem cell
Disease modeling
030104 developmental biology
Neural development
030220 oncology & carcinogenesis
Autism
Single-Cell Analysis
Neuroscience
Gene Deletion
Neurovetenskaper
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 383
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....acfc4ca5b200db9c5ce686f85ff3b6fa