Clonal dynamics in early human embryogenesis inferred from somatic mutation

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dc.contributor.authorPark, Seongyeolko
dc.contributor.authorMali, Nanda Mayako
dc.contributor.authorKim, Ryulko
dc.contributor.authorChoi, Jeong-Wooko
dc.contributor.authorLee, Junehawkko
dc.contributor.authorLim, Joonohko
dc.contributor.authorPark, Jung Minko
dc.contributor.authorPark, Jung Wooko
dc.contributor.authorKim, Donghyunko
dc.contributor.authorKim, Taewooko
dc.contributor.authorYi, Kijongko
dc.contributor.authorChoi, June Hyugko
dc.contributor.authorKwon, Seong Gyuko
dc.contributor.authorHong, Joo Heeko
dc.contributor.authorYouk, Jeonghwanko
dc.contributor.authorAn, Yohanko
dc.contributor.authorKim, Su Yeonko
dc.contributor.authorOh, Soo A.ko
dc.contributor.authorKwon, Youngohko
dc.contributor.authorHong, Dongwanko
dc.contributor.authorKim, Moonkyuko
dc.contributor.authorKim, Dong Sunko
dc.contributor.authorPark, Ji Youngko
dc.contributor.authorOh, Ji Wonko
dc.contributor.authorJu, Young Seokko
dc.date.accessioned2021-09-24T05:10:30Z-
dc.date.available2021-09-24T05:10:30Z-
dc.date.created2021-08-31-
dc.date.created2021-08-31-
dc.date.created2021-08-31-
dc.date.created2021-08-31-
dc.date.issued2021-09-
dc.identifier.citationNATURE, v.597, no.7876, pp.393-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10203/287822-
dc.description.abstractCellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos(1). 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.-
dc.languageEnglish-
dc.publisherNATURE PORTFOLIO-
dc.titleClonal dynamics in early human embryogenesis inferred from somatic mutation-
dc.typeArticle-
dc.identifier.wosid000688398800006-
dc.identifier.scopusid2-s2.0-85113501542-
dc.type.rimsART-
dc.citation.volume597-
dc.citation.issue7876-
dc.citation.beginningpage393-
dc.citation.publicationnameNATURE-
dc.identifier.doi10.1038/s41586-021-03786-8-
dc.contributor.localauthorJu, Young Seok-
dc.contributor.nonIdAuthorMali, Nanda Maya-
dc.contributor.nonIdAuthorChoi, Jeong-Woo-
dc.contributor.nonIdAuthorLee, Junehawk-
dc.contributor.nonIdAuthorPark, Jung Min-
dc.contributor.nonIdAuthorPark, Jung Woo-
dc.contributor.nonIdAuthorKim, Donghyun-
dc.contributor.nonIdAuthorKim, Taewoo-
dc.contributor.nonIdAuthorChoi, June Hyug-
dc.contributor.nonIdAuthorKwon, Seong Gyu-
dc.contributor.nonIdAuthorHong, Joo Hee-
dc.contributor.nonIdAuthorOh, Soo A.-
dc.contributor.nonIdAuthorKwon, Youngoh-
dc.contributor.nonIdAuthorHong, Dongwan-
dc.contributor.nonIdAuthorKim, Moonkyu-
dc.contributor.nonIdAuthorKim, Dong Sun-
dc.contributor.nonIdAuthorPark, Ji Young-
dc.contributor.nonIdAuthorOh, Ji Won-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusMITOCHONDRIAL-DNA HETEROPLASMY-
dc.subject.keywordPlusHUMAN BLASTOCYST-
dc.subject.keywordPlusGENETIC BOTTLENECK-
dc.subject.keywordPlusCELL LINEAGE-
dc.subject.keywordPlusCOPY NUMBER-
dc.subject.keywordPlusSTEM-CELLS-
dc.subject.keywordPlusSIGNATURES-
dc.subject.keywordPlusLANDSCAPE-
dc.subject.keywordPlusDISCOVERY-
dc.subject.keywordPlusFRAMEWORK-
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