Clonal dynamics of haematopoiesis across the human lifespan.

ABSTRACT: Age-related change in human haematopoiesis causes reduced regenerative capacity¹, cytopenias², immune dysfunction³ and increased risk of blood cancer^4-6, 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

SUBMITTER: Mitchell E 

PROVIDER: S-EPMC9177428 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature