Single-cell sperm transcriptomes and variants from fathers of children with and without autism spectrum disorder.
Molecular medicine
Predictive markers
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
08
2019
accepted:
02
01
2020
entrez:
6
3
2020
pubmed:
7
3
2020
medline:
7
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32133155
doi: 10.1038/s41525-020-0117-4
pii: 117
pmc: PMC7035312
doi:
Types de publication
Journal Article
Langues
eng
Pagination
14Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsC.E.M. is a cofounder and board member for Biotia and Onegevity Health, as well as an advisor or compensated speaker for Abbvie, Acuamark Diagnostics, ArcBio, BioRad, DNA Genotek, Genialis, Genpro, Karius, Illumina, New England Biolabs, QIAGEN, Whole Biome and Zymo Research. D.T., J.A.R. and C.E.M. have a related U.S. Patent application 62/460,480. The remaining authors declare that there are no competing interests.
Références
Biol Reprod. 2019 Jun 1;100(6):1661-1672
pubmed: 30951591
Neuron. 2011 Jun 9;70(5):863-85
pubmed: 21658581
Nat Biotechnol. 2014 Sep;32(9):915-925
pubmed: 25150835
Hum Reprod. 2011 Dec;26(12):3401-12
pubmed: 21989093
PLoS One. 2011 Feb 17;6(2):e16715
pubmed: 21379579
Mol Hum Reprod. 2011 Dec;17(12):721-6
pubmed: 21831882
Fertil Steril. 1995 Mar;63(3):591-7
pubmed: 7851592
Nat Biotechnol. 2016 Mar;34(3):303-11
pubmed: 26829319
Biochem Biophys Res Commun. 2000 Dec 9;279(1):213-8
pubmed: 11112441
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601
Syst Biol Reprod Med. 2013 Oct;59(5):287-95
pubmed: 23869956
CNS Neurol Disord Drug Targets. 2016;15(5):533-43
pubmed: 27071790
Exp Cell Res. 1996 Jun 15;225(2):374-81
pubmed: 8660926
Hum Reprod Update. 2013 Nov-Dec;19(6):604-24
pubmed: 23856356
Nucleic Acids Res. 2013 Apr;41(7):4104-17
pubmed: 23471003
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Neurobiol Learn Mem. 2013 Oct;105:93-9
pubmed: 23707798
Mol Reprod Dev. 2015 Jan;82(1):26-35
pubmed: 25536093
Nat Commun. 2019 Aug 14;10(1):3660
pubmed: 31413257
Nat Rev Genet. 2005 Aug;6(8):633-42
pubmed: 16136654
Proc Biol Sci. 2012 Jul 7;279(1738):2636-44
pubmed: 22378807
J Biol Chem. 2003 Aug 8;278(32):29471-7
pubmed: 12775710
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Genet. 2016 Feb;48(2):126-133
pubmed: 26656846
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Asian J Androl. 2011 Sep;13(5):764-8
pubmed: 21725332
Nat Genet. 2015 Jul;47(7):822-826
pubmed: 25985141
Mol Hum Reprod. 2003 Jun;9(6):331-6
pubmed: 12771233
Front Genet. 2019 Mar 01;10:8
pubmed: 30881372
Front Neurosci. 2017 Jan 05;10:601
pubmed: 28105001