Early divergence of mutational processes in human fetal tissues

Ewart Kuijk, Francis Blokzijl, Myrthe Jager, Nicolle Besselink, Sander Boymans, Susana M Chuva de Sousa Lopes, Ruben van Boxtel, Edwin Cuppen

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article numbereaaw1271
JournalScience advances
Issue number5
Publication statusPublished - May 2019


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