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Science, 07 Dec 2017: eaan8690 | DOI: 10.1126/science.aan8690
Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis
Taejeong Bae1, Livia Tomasini2, Jessica Mariani2, Bo Zhou3, Tanmoy Roychowdhury1, Daniel Franjic4, Mihovil Pletikos4, Reenal Pattni3, Bo-Juen Chen5, Elisa Venturini5, Bridget Riley-Gillis5, Nenad Sestan4,6, Alexander E. Urban3, Alexej Abyzov1,*, Flora M. Vaccarino2,4,6,*
1Mayo Clinic, Department of Health Sciences Research, Rochester, MN 55905, USA.
1Mayo Clinic, Department of Health Sciences Research, Rochester, MN 55905, USA.
2Yale University, Child Study Center, Yale University, New Haven, CT 06520, USA.
3Stanford University, Departments of Psychiatry and Genetics, Palo Alto, CA 94305, USA.
4Yale University, Department of Neuroscience, New Haven, CT 06520, USA.
5New York Genome Center, New York, NY 10013, USA.
6Yale Kavli Institute for Neuroscience, New Haven, CT 06520, USA.
*Corresponding author : Alexej Abyzov Flora M. Vaccarino
*Corresponding author : Alexej Abyzov Flora M. Vaccarino
Abstract
Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks post-conception) using clonal cell populations. We detected 200-400 single nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were shared with the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five post-zygotic cleavages and calculated a mutation rate of ~1.3 per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted toward oxidative damage and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit drastically more mutagenesis than adulthood.
논문정보
- Research article
- 2017년 12월 (BRIC 등록일 2018-01-08)
- 국외 연구진
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