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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
Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
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2019 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 383, no 1, article id UNSP 111469Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 383, no 1, article id UNSP 111469
Keywords [en]
Autism spectrum disorder, Neurexin, Neurexin-1 alpha, Induced pluripotent stem cell, Neural stem cell, Single cell RNA sequencing, Neural development, Disease modeling
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-395420DOI: 10.1016/j.yexcr.2019.06.014ISI: 000486736600011PubMedID: 31302032OAI: oai:DiVA.org:uu-395420DiVA, id: diva2:1363006
Funder
Swedish Foundation for Strategic Research , IB13-0074Swedish Research Council, 2015-02424Swedish Research Council, D0886501Swedish Research Council, 2017-03407Available from: 2019-10-22 Created: 2019-10-22 Last updated: 2019-10-22Bibliographically approved

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