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Asymmetric Contribution of Blastomere Lineages of First Division of the Zygote to Entire Human Body Using Post-Zygotic Variants

Authors
 Seong Gyu Kwon  ;  Geon Hue Bae  ;  June Hyug Choi  ;  Nanda Maya Mali  ;  Mee Sook Jun  ;  Dong Sun Kim  ;  Man-Hoon Han  ;  Seongyeol Park  ;  Young Seok Ju  ;  Seock Hwan Choi  ;  Ji Won Oh 
Citation
 TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol.19(4) : 809-821, 2022-08 
Journal Title
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
ISSN
 1738-2696 
Issue Date
2022-08
MeSH
Blastomeres* ; Human Body ; Humans ; Phylogeny ; Zygote*
Keywords
Asymmetry ; Clonal expansion ; Early embryonic mutations ; Lineage tracing ; Mutation filtering ; Somatic mutation
Abstract
Background: In humans, after fertilization, the zygote divides into two 2n diploid daughter blastomeres. During this division, DNA is replicated, and the remaining mutually exclusive genetic mutations in the genome of each cell are called post-zygotic variants. Using these somatic mutations, developmental lineages can be reconstructed. How these two blastomeres are contributing to the entire body is not yet identified. This study aims to evaluate the cellular contribution of two blastomeres of 2-cell embryos to the entire body in humans using post-zygotic variants based on whole genome sequencing.

Methods: Tissues from different anatomical areas were obtained from five donated cadavers for use in single-cell clonal expansion and bulk target sequencing. After conducting whole genome sequencing, computational analysis was applied to find the early embryonic mutations of each clone. We developed our in-house bioinformatics pipeline, and filtered variants using strict criteria, composed of mapping quality, base quality scores, depth, soft-clipped reads, and manual inspection, resulting in the construction of embryological phylogenetic cellular trees.

Results: Using our in-house pipeline for variant filtering, we could extract accurate true positive variants, and construct the embryological phylogenetic trees for each cadaver. We found that two daughter blastomeres, L1 and L2 (lineage 1 and 2, respectively), derived from the zygote, distribute unequally to the whole body at the clonal level. From bulk target sequencing data, we validated asymmetric contribution by means of the variant allele frequency of L1 and L2. The asymmetric contribution of L1 and L2 varied from person to person.

Conclusion: We confirmed that there is asymmetric contribution of two daughter blastomeres from the first division of the zygote across the whole human body.
Full Text
https://link.springer.com/article/10.1007/s13770-022-00443-7
DOI
10.1007/s13770-022-00443-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Oh, Ji Won(오지원) ORCID logo https://orcid.org/0000-0001-5742-5120
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190691
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