Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy.
Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy.
复制标题
在伴有透明质性星形细胞病的癫痫病例中，通过 snRNA-seq 解析了嵌合染色体 1q 的细胞类型特异性。
DOI：
10.1101/2023.10.16.562560
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Upadhyay,Vaibhav
中科院分区：
文献类型：
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作者：
Leng,Kun;Cadwell,CathrynR;PatrickDevine,W;Tihan,Tarik;Qi,Zhongxia;Singhal,Nilika;Glenn,Orit;Kamiya,Sherry;Wiita,Arun;Berger,Amy;Shieh,JosephT;Titus,ErronW;Paredes,MercedesF;Upadhyay,Vaibhav
目的染色体1q镶嵌增益（chr1q）与皮质发育畸形（MCD）和癫痫有关。透明质星形细胞病（HPA）是一种罕见的神经病理发现的癫痫与MCD的情况下。脑嵌合chr1q获得的细胞类型特异性和HPA的分子特征尚不清楚。方法我们报告1例耐药癫痫患儿，分别在3岁和5岁时行癫痫病灶切除，发现嵌合chr1q增加和HPA。我们对第二次切除的脑组织进行了单核RNA测序（snRNA-seq）。结果snrna -seq结果显示，chr1q基因在神经元和星形胶质细胞亚群中特异性表达增加。与推断的chr1q增益相关的差异表达基因包括akt3和与细胞粘附或迁移相关的基因。星形胶质细胞亚群显示突触相关转录物显著富集，这可能与HPA中观察到的星形细胞包涵体有关。snrna -seq可用于推断马赛克染色体拷贝数变化的细胞型特异性，并鉴定相关的基因表达改变，在chr1q获得的情况下，这可能涉及细胞迁移的畸变。未来使用空间谱分析的研究可以进一步了解HPA的分子特征。
ObjectivesMosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathologic finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown.MethodsWe present the case of a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA sequencing (snRNA-seq) of brain tissue from the second resection.ResultssnRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain includedAKT3and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA.DiscussionsnRNA-seq may be used to infer the cell-type specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.