Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis

Taejeong Bae, Livia Tomasini, Jessica Mariani, Bo Zhou, Tanmoy Roychowdhury, Daniel Franjic, Mihovil Pletikos, Reenal Pattni, Bo Juen Chen, Elisa Venturini, Bridget Riley-Gillis, Nenad Sestan, Alexander E. Urban, Alexej Abyzov, Flora M. Vaccarino

Research output: Contribution to journalArticle

67 Scopus citations

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 postconception) using clonal cell populations. We detected 200 to 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 also present in the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five postzygotic cleavages and calculated a mutation rate of ~1.3 mutations 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 substantially more mutagenesis than adulthood.

Original languageEnglish (US)
Pages (from-to)550-555
Number of pages6
JournalScience
Volume359
Issue number6375
DOIs
StatePublished - Feb 2 2018

ASJC Scopus subject areas

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    Bae, T., Tomasini, L., Mariani, J., Zhou, B., Roychowdhury, T., Franjic, D., Pletikos, M., Pattni, R., Chen, B. J., Venturini, E., Riley-Gillis, B., Sestan, N., Urban, A. E., Abyzov, A., & Vaccarino, F. M. (2018). Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science, 359(6375), 550-555. https://doi.org/10.1126/science.aan8690