E-viri
Recenzirano
Odprti dostop
-
Khan, Themasap A; Revah, Omer; Gordon, Aaron; Yoon, Se-Jin; Krawisz, Anna K; Goold, Carleton; Sun, Yishan; Kim, Chul Hoon; Tian, Yuan; Li, Min-Yin; Schaepe, Julia M; Ikeda, Kazuya; Amin, Neal D; Sakai, Noriaki; Yazawa, Masayuki; Kushan, Leila; Nishino, Seiji; Porteus, Matthew H; Rapoport, Judith L; Bernstein, Jonathan A; O'Hara, Ruth; Bearden, Carrie E; Hallmayer, Joachim F; Huguenard, John R; Geschwind, Daniel H; Dolmetsch, Ricardo E; Paşca, Sergiu P
Nature medicine, 12/2020, Letnik: 26, Številka: 12Journal Article
22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids. Transcriptional profiling across 100 days showed high reliability of differentiation and revealed changes in neuronal excitability-related genes. Using electrophysiology and live imaging, we identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons. The calcium deficit was related to resting membrane potential changes that led to abnormal inactivation of voltage-gated calcium channels. Heterozygous loss of DGCR8 recapitulated the excitability and calcium phenotypes and its overexpression rescued these defects. Moreover, the 22q11DS calcium abnormality could also be restored by application of antipsychotics. Taken together, our study illustrates how stem cell derived models can be used to uncover and rescue cellular phenotypes associated with genetic forms of neuropsychiatric disease.
Avtor
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.