量化的DA亚型脆弱性PD-associated变性。火山,情节展示或德文和罗斯福计算(方法)为每个68集群中确定SNpc snRNA-seq分析。那些明显标记集群(FDR-adjusted P < 0.05)增加或减少与PD /小黑裙。点和文本颜色的主要细胞类型:深绿色DA神经元;黄色,小胶质细胞/巨噬细胞;紫色,信息公开化;亮绿色叶,内皮细胞/周;粉红色的,星形胶质细胞。b,或者德文十多巴胺能神经被估计。中心杆对应或德文估计获得,宽度对应于南达科他州2.5×。 of OR estimate from MASC. Bars that cross zero (dotted line) not statistically significant (FDR-adjusted P > 0.05, n = 22,048 DA neurons sampled across ten PD/LBD donors and eight neurotypical donors). c, Left: disease enrichment score (Methods) overlaid onto a binned UMAP representation of integrative analysis of both PD/LBD and control DA neurons (n = 10 PD/LBD individuals and n = 8 neurotypical controls). Right: expression of selected genes used to validate subtype vulnerability plotted on UMAP representation of DA neurons. d, Representative images of triple-positive cells for a disease-resistant DA population (TH+/ CALB1+/ TMEM200A+人口(TH)和disease-vulnerable+/ AGTR1+/ SOX6+,底部)。白色/黑色星号指示neuromelanin-induced自体荧光,而白色箭头显示lipofuscin-induced自体荧光;灰色箭头表示RNA puncta。规模的酒吧、10μm。e,箱线图显示四大人口的比例在十PD和十控制SNpc组织捐助者,由两个染色计数smFISH图像程序(3258年和2081年DA神经元数为第一和第二试验,分别)中描述的d。中心行箱线图表明中值,而上下铰链表示数据的第一和第三个四分位数,分别。须上下铰链之间的距离代表≤1.5×四分位范围。所有的点代表每个亚型个案TH总额的一小部分+细胞数。+阳性标记;−-标记;纳米,而不是测量;NS,不重要。* P < 0.05 (P = 0.041 CALB1+/ TMEM200A+/ TH+CALB1比较,P = 0.028+/ TMEM200A−/ TH+CALB1比较,P = 0.009+/ TH+SOX6比较,P = 0.024+/ AGTR1+/ TH+SOX6比较,P = 0.28+/ AGTR1- - - - - -/ TH+实验和SOX6 P = 0.015+/ AGTR1−/ TH+比较;Wilcoxon rank-sum双边测试;方法)。信贷:自然神经科学(2022)。DOI: 10.1038 / s41593 - 022 - 01061 - 1
