Single-cell transcriptomic analysis in Noonan syndrome-derived brain organoids누난 증후군 환자 유래 뇌 오가노이드에서의 단일세포 전사체 분석

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Noonan syndrome (NS) is an autosomal dominant genetic disorder, dominantly caused by mutations in tyrosine phosphatase SHP2. Although NS patients frequently have a variety of neurological symptoms reported, it is still unclear how SHP2 mutations cause the neurodevelopmental abnormalities linked to this syndrome. Here, I report that NS-induced pluripotent stem cells (iPSCs) show abnormal development of excitatory neurons (ENs) in the differentiation process into cortical organoids (NS-COs). Although these organoids exhibit normal appearance, single-cell RNA sequencing uncovered that the EN population have been increased and several cortical layer markers are overexpressed in a patient-specific manner. Furthermore, upper layer marker SATB2 and the deep layer maker CTIP2 was co-expressed in the subpopulation of NS-ENs. In accordance with these findings, synaptic connections were also reduced in NS-COs. Collectively, our findings suggest that perturbed cortical layer identity and impeded neuronal connectivity contribute to the neurological manifestations of NS.
Advisors
Han, Yong-Mahnresearcher한용만researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2023
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2023.2,[iv, 100 p. :]

Keywords

Noonan syndrome▼ainduced pluripotent stem cells▼agenetic modification▼abrain organoid▼asingle-cell RNA sequencing▼aneurogenesis▼acortical layer; 누난 증후군▼a역분화 줄기세포▼a유전자 교정▼a뇌 오가노이드▼a단일세포 전사체 분석▼a신경발생▼a대뇌피질

URI
http://hdl.handle.net/10203/308468
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=1030419&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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