Clonal dynamics of haematopoiesis across the human lifespan

Mitchell, Emily; Chapman, Michael Spencer; Williams, Nicholas; Dawson, Kevin J.; Mende, Nicole; Calderbank, Emily F.; Jung, Hyunchul; Mitchell, Thomas J.; Coorens, Tim; Spencer, David H.; Machado, Heather E.; Lee-Six, Henry; Davies, Megan; Hayler, Daniel; Fabre, Margarete A.; Mahbubani, Krishnaa T.; Abascal, Federico; Cagan, Alex; Vassiliou, George S.; Baxter, E. Joanna; Martincorena, Iñigo; Stratton, Michael R.; Kent, David G.; Chatterjee, Krishna; Saeb‐Parsy, Kourosh; Green, Anthony R.; Nangalia, Jyoti; Laurenti, Elisa; Campbell, Peter J.

doi:10.1038/s41586-022-04786-y

articleNatureJun 1, 2022HYBRID OA

Clonal dynamics of haematopoiesis across the human lifespan

EMEmily Mitchell MSMichael Spencer Chapman NWNicholas Williams KJKevin J. Dawson NMNicole Mende

Wellcome/MRC Cambridge Stem Cell Institute · University of Cambridge · +5 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

, but the reason for such abrupt functional decline after 70 years of age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies of haematopoietic cells across 10 human subjects from 0 to 81 years of age. Haematopoietic stem cells or multipotent progenitors (HSC/MPPs) accumulated a mean of 17 mutations per year after birth and lost 30 base pairs per year of telomere length. Haematopoiesis in adults less than 65 years of age was massively polyclonal, with high clonal diversity and a stable population of 20,000-200,000 HSC/MPPs contributing evenly to blood production. By contrast, haematopoiesis in individuals aged over 75 showed profoundly decreased clonal diversity. In each of the…

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Topics & keywords

Topics

Keywords

Haematopoiesis
Biology
Stem cell
Population
Progenitor cell
Genetics
Immunology
Andrology

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