Population dynamics of normal human blood inferred from somatic mutations

作者：Lee-Six, Henry; Obro, Nina Friesgaard; Shepherd, Mairi S.; Grossmann, Sebastian; Dawson, Kevin; Belmonte, Miriam; O**orne, Robert J.; Huntly, Brian J. P.; Martincorena, Inigo; Anderson, Elizabeth; O'Neill, Laura; Stratton, Michael R.; Laurenti, Elisa; Green, Anthony R.^*; Kent, David G.^*; Campbell, Peter J.^*

来源：Nature, 2018, 561(7724): 473-+.

DOI：10.1038/s41586-018-0497-0

• HEMATOPOIETIC STEM-CELLS
• CHRONIC MYELOCYTIC-LEUKEMIA
• CLONAL HEMATOPOIESIS
• IN-VIVO
• MARROW-CELLS
• PATTERNS
• ORIGIN
• TRACKING
• COMMON
• RATES

Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree; all blood cells were derived from a common ancestor that preceded gastrulation. The size of the stem cell population grew steadily in early life, reaching a stable plateau by adolescence. We estimate the numbers of haematopoietic stem cells that are actively making white blood cells at any one time to be in the range of 50,000-200,000. We observed adult haematopoietic stem cell clones that generate multilineage outputs, including granulocytes and B lymphocytes. Harnessing naturally occurring mutations to report the clonal architecture of an organ enables the high-resolution reconstruction of somatic cell dynamics in humans.

• 出版日期2018-9-27