Reconstruction of human phylogenetic trees using single-cell genome sequencing

The trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes of embryonic cells remain to be largely unknown due to the technical and ethical challenges. Here we sequenced whole-genomes single-cell-derived clones and various bulk tissues dissected from entire human bodies. Using the discovered somatic mutations as an intrinsic barcode, we reconstructed cellular phylogenetic trees that provide novel insights into early human embryogenesis.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001007032	Human single cells were clonally expanded by culture and whole-genome sequenced. This dataset includes 334 clonal samples and 7 blood bulks from seven individuals (DB2, DB3, DB5, DB6, DB8, DB9, DB10). We extracted genomic DNA materials from clonally expanded cells and matched peripheral blood using DNeasy Blood and Tissue kits (Qiagen) according to the protocol. DNA libraries for WGS were generated by an Accel-NGS 2S Plus DNA Library Kit (Swift Biosciences) from 1 µg of genomic DNA materials. WGS was performed on either the Illumina HiSeq X platform or the NovaSeq 6000 platform to generate mean coverage of 25.2X for 374 clonally expanded cells and 94.8X for 7 matched blood tissues.	Illumina NovaSeq 6000	240
EGAD00001007704	To estimate the contribution of early embryogenic cell lineages in adult tissues, we performed deep targeted sequencing on 379 bulk tissues from various organs of the five individuals (DB3, DB6, DB8, DB9, DB10). Of the 441 early embryonic mutations targeted, 411 mutations could have high-quality baits designed for them. DNA libraries were prepared by SureSelectXT Library Prep Kit (Agilent), hybridized to the appropriate capture panel, multiplexed on flow cells, and subjected to paired-end sequencing (150-bp reads) on the NovaSeq 6000 platform (Illumina) with a mean ~2,900x depth of coverage for the early mutations. Sequence reads were trimmed and mapped to the human reference genome (GRCh37) using the BWA-MEM algorithm.	unspecified	379

Publications	Citations
Analysis of Differentiation Protocols Defines a Common Pancreatic Progenitor Molecular Signature and Guides Refinement of Endocrine Differentiation. Wesolowska-Andersen A, Jensen RR, Alcántara MP, Beer NL, Duff C, Nylander V, Gosden M, Witty L, Bowden R, McCarthy MI, Hansson M, Gloyn AL, Honore C. Stem Cell Reports 14: 2020 138-153	15
Asymmetric Contribution of Blastomere Lineages of First Division of the Zygote to Entire Human Body Using Post-Zygotic Variants. Kwon SG, Bae GH, Choi JH, Mali NM, Jun MS, Kim DS, Han MH, Park S, Ju YS, Choi SH, Oh JW. Tissue Eng Regen Med 19: 2022 809-821	0
Mitochondrial DNA mosaicism in normal human somatic cells. An J, Nam CH, Kim R, Lee Y, Won H, Park S, Lee WH, Park H, Yoon CJ, An Y, Kim JH, Jun JK, Bae JM, Shin EC, Kim B, Cha YJ, Kwon HW, Oh JW, Park JY, Kim MJ, Ju YS. Nat Genet 56: 2024 1665-1677	1