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

35 Citations (Scopus)

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.

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

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Neurogenesis
Nucleotides
Mutation Rate
Mutagenesis
Genome
Mosaicism
Brain
Cell Lineage
Prosencephalon
Cell Division
Embryonic Development
Neoplasms
Fetus
Spleen
Neurons
Mutation
Population

ASJC Scopus subject areas

  • General

Cite this

Bae, T., Tomasini, L., Mariani, J., Zhou, B., Roychowdhury, T., Franjic, D., ... 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

Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. / Bae, Taejeong; Tomasini, Livia; Mariani, Jessica; Zhou, Bo; Roychowdhury, Tanmoy; Franjic, Daniel; Pletikos, Mihovil; Pattni, Reenal; Chen, Bo Juen; Venturini, Elisa; Riley-Gillis, Bridget; Sestan, Nenad; Urban, Alexander E.; Abyzov, Alexej; Vaccarino, Flora M.

In: Science, 07.12.2017, p. 1-10.

Research output: Contribution to journalArticle

Bae, T, Tomasini, L, Mariani, J, Zhou, B, Roychowdhury, T, Franjic, D, Pletikos, M, Pattni, R, Chen, BJ, Venturini, E, Riley-Gillis, B, Sestan, N, Urban, AE, Abyzov, A & Vaccarino, FM 2017, 'Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis', Science, pp. 1-10. https://doi.org/10.1126/science.aan8690
Bae T, Tomasini L, Mariani J, Zhou B, Roychowdhury T, Franjic D et al. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science. 2017 Dec 7;1-10. https://doi.org/10.1126/science.aan8690
Bae, Taejeong ; Tomasini, Livia ; Mariani, Jessica ; Zhou, Bo ; Roychowdhury, Tanmoy ; Franjic, Daniel ; Pletikos, Mihovil ; Pattni, Reenal ; Chen, Bo Juen ; Venturini, Elisa ; Riley-Gillis, Bridget ; Sestan, Nenad ; Urban, Alexander E. ; Abyzov, Alexej ; Vaccarino, Flora M. / Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. In: Science. 2017 ; pp. 1-10.
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