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

52 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
StateAccepted/In press - Dec 7 2017


ASJC Scopus subject areas

  • General

Cite this

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. (Accepted/In press). Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science, 1-10. https://doi.org/10.1126/science.aan8690