Clonal dynamics in early human embryogenesis inferred from somatic mutation

Seongyeol Park, Nanda Maya Mali, Ryul Kim, Jeong-Woo Choi, Junehawk Lee, Joonoh Lim, Jung Min Park, Jung Woo Park, Donghyun Kim, Taewoo Kim, Kijong Yi, June Hyug Choi, Seong Gyu Kwon, Joo Hee Hong, Jeonghwan Youk, Yohan An, Su Yeon Kim, Soo A Oh, Youngoh Kwon, Dongwan Hong, Moonkyu Kim, Dong Sun Kim, Ji Young Park, Ji Won Oh () and Young Seok Ju ()
Additional contact information
Seongyeol Park: Korea Advanced Institute of Science and Technology (KAIST)
Nanda Maya Mali: Kyungpook National University
Ryul Kim: Korea Advanced Institute of Science and Technology (KAIST)
Jeong-Woo Choi: Kyungpook National University
Junehawk Lee: Korea Institute of Science and Technology Information (KISTI)
Joonoh Lim: Korea Advanced Institute of Science and Technology (KAIST)
Jung Min Park: Kyungpook National University
Jung Woo Park: Korea Institute of Science and Technology Information (KISTI)
Donghyun Kim: Kyungpook National University
Taewoo Kim: Korea Advanced Institute of Science and Technology (KAIST)
Kijong Yi: Korea Advanced Institute of Science and Technology (KAIST)
June Hyug Choi: Kyungpook National University
Seong Gyu Kwon: Kyungpook National University
Joo Hee Hong: Kyungpook National University
Jeonghwan Youk: Korea Advanced Institute of Science and Technology (KAIST)
Yohan An: Korea Advanced Institute of Science and Technology (KAIST)
Su Yeon Kim: Korea Advanced Institute of Science and Technology (KAIST)
Soo A Oh: Korea Advanced Institute of Science and Technology (KAIST)
Youngoh Kwon: GENOME INSIGHT Inc
Dongwan Hong: Catholic University of Korea
Moonkyu Kim: Kyungpook National University
Dong Sun Kim: Kyungpook National University
Ji Young Park: Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University
Ji Won Oh: Kyungpook National University
Young Seok Ju: Korea Advanced Institute of Science and Technology (KAIST)

Nature, 2021, vol. 597, issue 7876, 393-397

Abstract: Abstract Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03786-8 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:597:y:2021:i:7876:d:10.1038_s41586-021-03786-8

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03786-8

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().