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从iPSC衍生的健康人体天体细胞选择性地将针对神经元基因的miRNA加载到细胞外囊中

Sara Gordillo-Sampedro¹, Lina Antounians², Wei Wei³

¹Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Molecular and cellular neurosciences

|April 25, 2024

概括

健康的天体细胞释放出具有特定微RNA (miRNA) 载荷的细胞外囊泡 (EV). 这些EV可以作为神经发育障碍的生物标志物,如雷特综合征 (RTT),并通过RNA结合蛋白加载.

科学领域:

神经科学是一个神经科学.
细胞生物学细胞生物学
生物化学生物化学

背景情况:

星球细胞与神经元通信,影响大脑发育和功能.
天体细胞衍生的细胞外囊泡 (EVs) 携带着调节基因表达的微RNA (miRNA) 载荷.
天体细胞衍生因子的失调与神经发育障碍有关,包括雷特综合征 (RTT).

研究的目的:

为了表征人类天体细胞衍生EVs (ADEVs) 中的miRNA载荷和序列动机.
通过ADEV货物分析,识别神经发育障碍的潜在非侵入性生物标志物.
为了研究miRNA分类到ADEVs的机制.

主要方法:

人类诱导的多能干细胞 (iPSCs) 分化为星球细胞.
RNA测序 (RNA-Seq) 在星球细胞及其分泌的ADEVs上进行.
进行了miRNA向基因通路分析和RNA结合蛋白质动机分析.

主要成果:

与母星细胞相比,星细胞衍生的EVs (ADEVs) 含有不同的miRNA配置文件.
大约120个miRNA相对富含ADEV,这表明有活跃的分类机制.
动因分析确定了RNA结合蛋白 (FUS,SRSF7,CELF5) 的结合部位,miR-483-5p被ADEVs显著丰富.
miR-483-5p调节MECP2,这是一个涉及RTT的基因.

结论:

人类天体细胞衍生的EV (ADEV) 选择性地包装特定的miRNA,包括miR-483-5p.
RNA结合蛋白相互作用可能会调节miRNAs选择性加载到ADEV中.
ADEV及其miRNA载荷代表了像RTT这样的神经发育障碍的潜在的非侵入性生物标志物.

关键词:

星球细胞是星球细胞.血液中的生物标志物.细胞外囊泡中的细胞外囊泡.诱导的多能干细胞干细胞在RNA结合蛋白质中的RNA结合蛋白.雷特综合征是什么意思雷特综合征是什么意思在 miR-483-5p 中使用.这是一个微型RNA.

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