A whole genome analysis of single fetal human stem cells from the liver and the intestine

Mutations of embryonic and fetal origin have the potential to affect a large proportion of adult cells and may alter cancer predisposition or lead to genetic disease syndromes. We have recently shown that human adult-stem cells progressively acquire approximately 40 novel tissue-specific mutations per year throughout postnatal life. Prenatal mutation rates are as yet unknown. Here we determined genome-wide mutation patterns of single stem cells in human development by sequencing of clonally expanded intestinal and liver organoid cultures of 2nd trimester human foetuses. Our results show that mutation rates in fetal stem cells are significantly higher than in adult stem cells.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 3 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001003997	From 2nd trimester human foetuses we derived liver and intestinal stem cells. These were clonally expanded until enough material was available for whole genome sequencing. For each foetus, reference tissue (skin or bulk liver) was also sequenced to determine all germline variants. These were subtracted from the clones to determine all somatic mutations that had been acquired during embryonic and fetal development.	HiSeq X Ten NextSeq 500	50

Publications	Citations
Early divergence of mutational processes in human fetal tissues. Kuijk E, Blokzijl F, Jager M, Besselink N, Boymans S, Chuva de Sousa Lopes SM, van Boxtel R, Cuppen E. Sci Adv 5: 2019 eaaw1271	15
Mutation accumulation and developmental lineages in normal and Down syndrome human fetal haematopoiesis. Hasaart KAL, Manders F, van der Hoorn ML, Verheul M, Poplonski T, Kuijk E, de Sousa Lopes SMC, van Boxtel R. Sci Rep 10: 2020 12991	16
Human induced pluripotent stem cells display a similar mutation burden as embryonic pluripotent cells <i>in vivo</i>. Hasaart KAL, Manders F, Ubels J, Verheul M, van Roosmalen MJ, Groenen NM, Oka R, Kuijk E, Lopes SMCS, Boxtel RV. iScience 25: 2022 103736	4