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CDKL5 iPSC-derived Neural Cells Exhibit Deficiencies in Growth and Increased Apoptosis
Başlık:
CDKL5 iPSC-derived Neural Cells Exhibit Deficiencies in Growth and Increased Apoptosis
Yazar:
Kwok, Ellius, author.
ISBN:
9780438133457
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (56 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Alysson Muotri; Deborah Yelon Committee members: Christopher Armour.
Özet:
Cyclin-dependent kinase-like 5 (CDKL5) syndrome is a neurodevelopmental disorder that results in early-onset intractable seizures, mental retardation, and a host of autistic phenotypes. Although the role of CDKL5 is not well understood, previous studies have implicated it plays a crucial role within the AKT/mTOR pathways, which regulate cellular proliferation, apoptosis, and synaptogenesis. This study focused on generating neural progenitor cells (NPCs) and subsequently differentiating them into neurons, for the purpose of modeling the effects of CDKL5 mutations on the phenotypes listed above. hiPSC-derived CDKL5 NPCs exhibited decreased cell proliferation and increased apoptosis as compared to controls, which is congruent with the findings of previous studies with regards to inactivation of the AKT/mTOR pathways. Furthermore, hiPSC-derived CDKL5 neurons displayed no change in total dendritic length but appeared to grow more slowly during early neurodevelopment as compared to controls. These neurons also had a greater density of dendritic spines, with increased motility, as compared to controls. These findings conflict with the results from previous CDKL5 studies based on mouse knockout models. The discrepancy in results suggests that CDKL5 function may not be preserved across species, a claim that is supported by the fact that the murine models do not recapitulate the defining feature of CDKL5: early-onset intractable seizures.
Notlar:
School code: 0033
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(694453.1) | 694453-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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