Early divergence of mutational processes in human fetal tissues

Science Advances
Ewart KuijkEdwin Cuppen


A developing human fetus needs to balance rapid cellular expansion with maintaining genomic stability. Here, we accurately quantified and characterized somatic mutation accumulation in fetal tissues by analyzing individual stem cells from human fetal liver and intestine. Fetal mutation rates were about fivefold higher than in tissue-matched adult stem cells. The mutational landscape of fetal intestinal stem cells resembled that of adult intestinal stem cells, while the mutation spectrum of fetal liver stem cells is distinct from stem cells of the fetal intestine and the adult liver. Our analyses indicate that variation in mutational mechanisms, including oxidative stress and spontaneous deamination of methylated cytosines, contributes to the observed divergence in mutation accumulation patterns and drives genetic mosaicism in humans.


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May 20, 2020·Nature Communications·Ewart KuijkEdwin Cuppen
May 16, 2020·Annual Review of Genomics and Human Genetics·Alexej Abyzov, Flora M Vaccarino
Jun 21, 2020·Scientific Reports·Richard M CawthonLynn B Jorde
Feb 26, 2021·Nature Reviews. Cancer·Nobuyuki Kakiuchi, Seishi Ogawa
Mar 12, 2021·Nature·Tim H H CoorensSam Behjati
Nov 28, 2020·Trends in Cancer·Bruce GottliebGerald Batist
Aug 27, 2021·Nature·Tim H H CoorensMichael R Stratton

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Methods Mentioned

chromosomal aberrations
Illumina sequencing

Software Mentioned

Integrative Genomics Viewer ( IGV )
MutationalPatterns R package

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