TY - JOUR
T1 - Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis
AU - Bae, Taejeong
AU - Tomasini, Livia
AU - Mariani, Jessica
AU - Zhou, Bo
AU - Roychowdhury, Tanmoy
AU - Franjic, Daniel
AU - Pletikos, Mihovil
AU - Pattni, Reenal
AU - Chen, Bo Juen
AU - Venturini, Elisa
AU - Riley-Gillis, Bridget
AU - Sestan, Nenad
AU - Urban, Alexander E.
AU - Abyzov, Alexej
AU - Vaccarino, Flora M.
N1 - Publisher Copyright:
© The Authors 2017, some rights reserved
PY - 2018/2/2
Y1 - 2018/2/2
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aan8690
DO - 10.1126/science.aan8690
M3 - Article
C2 - 29217587
AN - SCOPUS:85037705979
SN - 0036-8075
VL - 359
SP - 550
EP - 555
JO - Science
JF - Science
IS - 6375
ER -