Author
Listed:
- Seongyeol Park
(Korea Advanced Institute of Science and Technology (KAIST)
GENOME INSIGHT Inc)
- Nanda Maya Mali
(Kyungpook National University)
- Ryul Kim
(Korea Advanced Institute of Science and Technology (KAIST))
- Jeong-Woo Choi
(Kyungpook National University
Immune Square Inc)
- 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
Immune Square Inc)
- Jung Woo Park
(Korea Institute of Science and Technology Information (KISTI))
- Donghyun Kim
(Kyungpook National University
Immune Square Inc)
- 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
Immune Square Inc
Kyungpook National University Hospital)
- Young Seok Ju
(Korea Advanced Institute of Science and Technology (KAIST)
GENOME INSIGHT Inc)
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.
Suggested Citation
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, 2021.
"Clonal dynamics in early human embryogenesis inferred from somatic mutation,"
Nature, Nature, vol. 597(7876), pages 393-397, September.
Handle:
RePEc:nat:nature:v:597:y:2021:i:7876:d:10.1038_s41586-021-03786-8
DOI: 10.1038/s41586-021-03786-8
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