期刊
EXPERIMENTAL CELL RESEARCH
卷 383, 期 1, 页码 -出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.06.014
关键词
Autism spectrum disorder; Neurexin; Neurexin-1 alpha; Induced pluripotent stem cell; Neural stem cell; Single cell RNA sequencing; Neural development; Disease modeling
资金
- Stiftelsen for strategisk forskning, SSF [IB13-0074]
- Swedish Research Council, Vetenskapsradet [2015-02424, D0886501, 2017-03407]
- Karolinska Institutet Doctoral funding
- Saystaholm Society
- Vinnova [2017-03407, 2015-02424] Funding Source: Vinnova
- Swedish Foundation for Strategic Research (SSF) [IB13-0074] Funding Source: Swedish Foundation for Strategic Research (SSF)
- Swedish Research Council [2017-03407, 2015-02424] Funding Source: Swedish Research Council
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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