Tomoiaga Delia, Aguiar-Pulido Vanessa, Shrestha Shristi, Feinstein Paul, Levy Shawn E, Mason Christopher E, Rosenfeld Jeffrey A
1Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY USA.
2The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY USA.
NPJ Genom Med. 2020 Feb 21;5:14. doi: 10.1038/s41525-020-0117-4. eCollection 2020.
The human sperm is one of the smallest cells in the body, but also one of the most important, as it serves as the entire paternal genetic contribution to a child. Investigating RNA and mutations in sperm is especially relevant for diseases such as autism spectrum disorders (ASD), which have been correlated with advanced paternal age. Historically, studies have focused on the assessment of bulk sperm, wherein millions of individual sperm are present and only high-frequency variants can be detected. Using 10× Chromium single-cell sequencing technology, we assessed the transcriptome from >65,000 single spermatozoa across six sperm donors (scSperm-RNA-seq), including two who fathered multiple children with ASD and four fathers of neurotypical children. Using RNA-seq methods for differential expression and variant analysis, we found clusters of sperm mutations in each donor that are indicative of the sperm being produced by different stem cell pools. Finally, we have shown that genetic variations can be found in single sperm.
人类精子是人体中最小的细胞之一，但也是最重要的细胞之一，因为它承载着父亲对孩子的全部遗传贡献。研究精子中的RNA和突变对于诸如自闭症谱系障碍（ASD）等疾病尤为重要，这些疾病与父亲的高龄有关。从历史上看，研究主要集中在对大量精子的评估上，其中存在数百万个单个精子，只能检测到高频变异。使用10×铬单细胞测序技术，我们评估了来自六个精子供体的超过65,000个单个精子的转录组（scSperm-RNA-seq），其中包括两个育有多个患有ASD孩子的父亲和四个育有神经典型孩子的父亲。使用RNA-seq方法进行差异表达和变异分析，我们在每个供体中发现了精子突变簇，这些突变簇表明精子是由不同的干细胞库产生的。最后，我们证明了在单个精子中可以发现基因变异。
