Kerepesi, Csaba and Gladyshev, Vadim N. (2023) Intersection clock reveals a rejuvenation event during human embryogenesis. AGING CELL, 22 (10). ISSN 1474-9718 10.1111/acel.13922

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Abstract

Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples and applied it to human embryo development data. We observed no changes in the predicted epigenetic age between cleavage stage and blastocyst stage embryos; however, a significant decrease was observed between blastocysts and cells representing the epiblast. Additionally, by applying the intersection clock to datasets spanning pre and postimplantation, we found no significant change in the epigenetic age during preimplantation stages; however, the epigenetic age of postimplantation samples was lower compared to the preimplantation stages. We further investigated the epigenetic age of primed (representing early postimplantation) and naive (representing preimplantation) pluripotent stem cells and observed that in all cases the epigenetic age of primed cells was significantly lower than that of naive cells. Together, our data suggest that human embryos are rejuvenated during early embryogenesis. Hence, the rejuvenation event is conserved between the mouse and human, and it occurs around the gastrulation stage in both species. Beyond this advance, the intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets as opposed to methylation arrays.We developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples. Using the new method, we revealed a rejuvenation event during human embryogenesis around the gastrulation stage. The intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets.image

Item Type:	Article
Uncontrolled Keywords:	Aging; Rejuvenation; Bisulfite sequencing; RRBS; WGBS; Epigenetic clock; Human embryogenesis;
Subjects:	Q Science > QA Mathematics and Computer Science > QA75 Electronic computers. Computer science / számítástechnika, számítógéptudomány
Divisions:	Informatics Laboratory
SWORD Depositor:	MTMT Injector
Depositing User:	MTMT Injector
Date Deposited:	17 Jan 2024 08:51
Last Modified:	17 Jan 2024 08:51
URI:	https://eprints.sztaki.hu/id/eprint/10676

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