Abstract
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.
References
Mar 1, 1995·Fertility and Sterility·S SmithL Scott
Jun 15, 1996·Experimental Cell Research·W S KistlerM Parvinen
Dec 9, 2000·Biochemical and Biophysical Research Communications·I A ZalenskayaA O Zalensky
May 29, 2003·Molecular Human Reproduction·Klaus StegerMartin Bergmann
May 31, 2003·The Journal of Biological Chemistry·Susan M Wykes, Stephen A Krawetz
Sep 2, 2005·Nature Reviews. Genetics·Stephen A Krawetz
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jul 21, 2010·Genome Research·Aaron McKennaMark A DePristo
Mar 8, 2011·PloS One·Mark D AlterDietrich A Stephan
Jun 11, 2011·Neuron·Stephan J SandersMatthew W State
Jul 5, 2011·Asian Journal of Andrology·María EncisoJaime Gosálvez
Aug 13, 2011·Molecular Human Reproduction·G D JohnsonS A Krawetz
Oct 13, 2011·Human Reproduction·Stephen A KrawetzMichael P Diamond
Mar 2, 2012·Proceedings. Biological Sciences·Bettina E FischerSteven Russell
Mar 9, 2013·Nucleic Acids Research·Edward SendlerStephen A Krawetz
May 28, 2013·Neurobiology of Learning and Memory·Mimi A Trinh, Eric Klann
Jul 17, 2013·Human Reproduction Update·Meritxell JodarUNKNOWN Reproductive Medicine Network
Jul 23, 2013·Systems Biology in Reproductive Medicine·Shihong MaoStephen A Krawetz
Aug 26, 2014·Nature Biotechnology·Sheng LiChristopher E Mason
Dec 24, 2014·Molecular Reproduction and Development·Elham Savadi-ShirazMohammad Reza Sadeghi
May 20, 2015·Nature Genetics·Laurent C FrancioliShamil R Sunyaev
Dec 15, 2015·Nature Genetics·Raheleh RahbariMatthew E Hurles
Feb 2, 2016·Nature Biotechnology·Grace X Y ZhengHanlee P Ji
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Jan 17, 2017·Nature Communications·Grace X Y ZhengJason H Bielas
Jan 21, 2017·Frontiers in Neuroscience·Ashley AnselBenjamin Gesundheit
Apr 3, 2018·Nature Biotechnology·Andrew ButlerRahul Satija
Mar 19, 2019·Frontiers in Genetics·Samantha L GoldmanChristopher E Mason
Apr 6, 2019·Biology of Reproduction·Romain LambrotSarah Kimmins