Modeling tuberous sclerosis with organoids.
Modeling tuberous sclerosis with organoids.
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用类器官模拟结节性硬化症。
DOI：
10.1126/science.abn6158
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Henske,ElizabethP
中科院分区：
文献类型：
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作者：
Ihrie,RebeccaA;Henske,ElizabethP
多发性硬化症（TSC）是一种破坏性疾病，其特征在于皮肤（血管纤维瘤）、脑（皮质结节、室管膜下结节（SEN）和室管膜下巨细胞星形细胞瘤（SEGA））、心脏（横纹肌瘤）、肺（淋巴管平滑肌瘤病（LAM））和肾（血管平滑肌脂肪瘤和肾细胞癌）的独特肿瘤。神经系统表现还可以包括癫痫发作和TSC相关的神经精神障碍，其包括攻击性行为、自闭症谱系障碍、智力残疾和精神障碍。TSC是由杂合生殖系突变引起的，这些突变会抑制TSC 1或TSC 2，而TSC 1或TSC 2通常会抑制雷帕霉素复合物1（mTORC 1）的机制靶点。mTORC1抑制剂用于治疗脑、肺和肾肿瘤和癫痫发作，但不能改善所有症状，并且关于脑肿瘤发生如何开始的不确定性仍然存在。在本期的第401页，Eichmülleret等人鉴定了一种产生皮质结节样和室管膜下肿瘤样细胞的前体细胞，增加了对TSC神经学表现的理解。
Tuberous sclerosis complex (TSC) is a devastating disease characterized by distinctive tumors of the skin (angiofibromas), brain [cortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs)], heart (rhabdomyomas), lungs [lymphangioleiomyomatosis (LAM)], and kidney (angiomyolipomas and renal cell carcinoma) . Neurologic manifestations can also include seizures and TSC-associated neuropsychiatric disorder, which encompasses aggressive behaviors, autism spectrum disorders, intellectual disability, and psychiatric disorders. TSC is caused by heterozygous germline mutations that inactivate TSC1 or TSC2, which normally inhibit mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 inhibitors are used for the treatment of brain, lung, and kidney tumors and seizures but do not improve all symptoms, and uncertainty persists about how brain tumorigenesis begins. On page 401 of this issue, Eichmülleret al.identify a precursor cell that generates cortical tuber–like and subependymal tumor–like cells, increasing the understanding of neurological manifestations of TSC.