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Most DNA-mark differences in human colon cells traced to embryos

By around age 60, a colorectal cell lineage had about 1.2 million DNA-mark differences from a reference pattern; about 60% dated to early embryos.

Paper by Young Seok Ju, Hyein Won, Dong-Sung Lee, 14 more authorsM P Jung · Korea Advanced Institute of Science and Technology
Colon lining and a nearby embryonic cell cluster share grouped DNA marks, beside a smaller gray tissue patch with differently spaced marks.
Preprint: cross-sectional study of 16 donors of colorectal epithelial cellsMechanisms

406 participants

Limit: Only 16 donors supplied the clones used to infer embryonic origins

Edited by Boris Djordjevic · AgingResearch.News

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An observational study analyzed 406 clones—groups grown from single cells lining the human colon and rectum—from 16 donors. Researchers read their DNA sequences and mapped DNA methylation, chemical marks on DNA that can influence gene activity.

By around age 60, a lineage of related colorectal cells had accumulated about 1.2 million methylation differences from the consensus pattern used for comparison. About 60% were established during early embryonic development and were stably passed on throughout life, rather than accumulating with age. These early differences often clustered in particular DNA regions. Researchers identified 14,402 regions with such developmental patterns. These patterns were often associated with differences in gene activity in the adult colorectal lining, suggesting that their functional effects may persist into adulthood.

Why it matters

Distinguishing developmental differences in DNA marks from changes acquired later could help researchers identify which patterns reflect aging.

Caveats

The associations with gene activity do not establish cause and effect. This preprint has not been peer-reviewed and analyzed cell-derived clones from 16 donors.