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Role of Nuclear-FGFR1 in Schizophrenia and Ontogenic Genome Programming - A Computational Study
Başlık:
Role of Nuclear-FGFR1 in Schizophrenia and Ontogenic Genome Programming - A Computational Study
Yazar:
Dhiman, Siddhartha, author. (orcid)0000-0001-6957-8765
ISBN:
9780438049901
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (82 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Includes supplementary digital materials.
Advisors: Michal K. Stachowiak Committee members: Anirban Dutta; Pinaki Sarder.
Özet:
Earlier studies from schizophrenia patients have shown that the disorder causes changes in the genome at proneuronal stage -- best progenitor cells commit to neural cells. In particular, the mRNA transcriptome nuclear FGFR1 (nFGFR1) was found to be dysregulated. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) derived cerebral organoid from four control and three schizophrenia patients were grown to model the first trimester of in utero brain development. These organoids were tagged to show Ki67 + neural progenitor cells (NPCs) and calretinin interneurons in the cortical plate (CP). Using computational algorithms to detect cells and characterize them, it was discovered that NPCs in schizophrenia modeled organoids abnormally in comparison to those in control organoids. The matured interneurons in the CP showed decreased intracortical connectivity denoted by changes in their orientation.
Further effects of nFGFR1 on the global genome programming were studied using fold change and correlational analyses. nFGFR1 was either under expressed or overexpressed using tyrosine kinase domain removal (TK-) or the addition of nuclear localization signal (+NLS) respectively, in both NPCs and NCCs. It was observed that nFGFR1 acts like a complex circuit comprising of a bandpass filter and a proportional (P) controller to modulate gene-gene coordination.
In addition, miRNA coordination was also analyzed in relation to mRNAs using similar correlational analyses to reveal that the entire genome maintains a homeostatic state that preserves the miRNA to mRNA control such that the constant of proportionality between them is unaffected by changes in genome.
Notlar:
School code: 0656
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(694162.1) | 694162-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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