한빛사논문
- 조회832
Seongyeol Park1,2,10, Nanda Maya Mali3,10, Ryul Kim1,10, Jeong-Woo Choi3,4, Junehawk Lee5, Joonoh Lim1, Jung Min Park3,4, Jung Woo Park5, Donghyun Kim3,4, Taewoo Kim1, Kijong Yi1, June Hyug Choi3, Seong Gyu Kwon3, Joo Hee Hong3, Jeonghwan Youk1, Yohan An1, Su Yeon Kim1, Soo A Oh1, Youngoh Kwon2, Dongwan Hong6, Moonkyu Kim7, Dong Sun Kim3, Ji Young Park8, Ji Won Oh3,4,9,11 & Young Seok Ju1,2,11
1Graduate School of Medical Science and Engineering (GSMSE), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
2GENOME INSIGHT Inc, Daejeon, Republic of Korea.
3Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
4Immune Square Inc, Daegu, Republic of Korea.
5Korea Institute of Science and Technology Information (KISTI), Daejeon, Republic of Korea.
6Department of Medical Informatics, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
7Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
8Department of Pathology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
9Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
10These authors contributed equally: Seongyeol Park, Nanda Maya Mali, Ryul Kim.
11These authors jointly supervised: Ji Won Oh, Young Seok Ju.
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.
논문정보
- Research article
- 2021년 08월 (BRIC 등록일 2021-08-27)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
관련 웨비나
![단일 세포 전장 유전체 시퀀싱을 통한 인간의 발생과정 추적 [Nature]](/upload/board/files/onseminar/thumb/thumb_0000342.png)
학술웨비나
단일 세포 전장 유전체 시퀀싱을 통한 인간의 발생과정 추적 [Nature] 최근 암세포가 아닌 정상세포에 누적된 체세포 돌연변이(somatic mutation)를 발굴하는 연구가 활발하게 이루어지고 있습니다. 정상 세포 조직은 암 조직과 달리 많은 수의 클론이 공존하기 때문에, 일반적인 방법으로는 체세포 돌연변이를 찾을 수 없고, 단일 세포로 분리한 후 시퀀싱을 해야 가능합니다. 이번 발표에서는 단일 세포를 분리하여 전장 유전체 시퀀싱(whole-genome sequencing)을 하는 다양한 전략을 소개하고, 본 연구팀에서 해당 방법을 활용하여 인간의 발생과정(human embryogenesis)을 추적한 연구의 방법과 내용을 소개할 예정입니다.- 박성열(KAIST)
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