Extensive phylogenies of human development inferred from somatic mutations.

Nature
Tim H H CoorensMichael R Stratton

Abstract

Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing1,2. Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the s...Continue Reading

References

Mar 1, 1977·Developmental Biology·J E Sulston, H R Horvitz
Mar 1, 2003·Proceedings of the National Academy of Sciences of the United States of America·Marco NovelliNick Wright
Apr 11, 2009·Nature·Michael R StrattonP Andrew Futreal
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Sep 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Peter Van LooVessela N Kristensen
Feb 12, 2011·Cytogenetic and Genome Research·T VoetJ R Vermeesch
May 23, 2012·Cell·Serena Nik-ZainalUNKNOWN Breast Cancer Working Group of the International Cancer Genome Consortium
Jul 23, 2013·Developmental Cell·Margarida SanchoTristan A Rodríguez
Jan 21, 2014·Bioinformatics·Moritz GerstungPeter J Campbell
Nov 6, 2014·Molecular Biology and Evolution·Lam-Tung NguyenBui Quang Minh
Dec 15, 2015·Nature Methods·Petr StrnadJan Ellenberg
Dec 9, 2016·Current Protocols in Bioinformatics·David JonesPeter J Campbell
Mar 23, 2017·Nature·Young Seok JuMichael R Stratton
Feb 3, 2018·BMC Evolutionary Biology·Diep Thi HoangBui Quang Minh
Mar 29, 2018·Nature·Anna AlemanyAlexander van Oudenaarden
Jul 25, 2018·Development·Toshihiro Kobayashi, M Azim Surani
Aug 19, 2018·Scientific Reports·Erikka LoftfieldMitchell J Machiela
Sep 7, 2018·Nature·Henry Lee-SixPeter J Campbell
Jun 1, 2019·Science Advances·Ewart KuijkEdwin Cuppen
Oct 28, 2019·Nature·Henry Lee-SixMichael R Stratton
Oct 28, 2019·Nature·Peter PriestleyEdwin Cuppen
Dec 7, 2019·Science·Tim H H CoorensSam Behjati
Jan 31, 2020·Nature·Kenichi YoshidaPeter J Campbell
May 1, 2020·Nature·Luiza MooreMichael R Stratton
Jun 26, 2020·Nature·Sarah J AitkenMartin S Taylor
Jul 23, 2020·Cell·Sigurgeir OlafssonCarl A Anderson
Aug 12, 2020·Nature Communications·Marta N ShahbaziMagdalena Zernicka-Goetz
Oct 3, 2020·Science·Andrew R J LawsonIñigo Martincorena
Nov 20, 2020·The New England Journal of Medicine·Tim H H CoorensSam Behjati
Mar 12, 2021·Nature·Tim H H CoorensSam Behjati
May 14, 2021·Nature·Michael Spencer ChapmanAna Cvejic
Aug 27, 2021·Nature·Luiza MooreRaheleh Rahbari

❮ Previous
Next ❯

Citations

Aug 27, 2021·Nature·Kamila Naxerova

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.