| Autor: |
Kreger, Jesse, Mooney, Jazlyn A., Shibata, Darryl, MacLean, Adam L. |
| Předmět: |
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| Zdroj: |
Nature Communications; 11/26/2024, Vol. 15 Issue 1, p1-12, 12p |
| Abstrakt: |
Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection indicating variants are acquired much earlier in life with unexplained initial growth spurts. Here we use fluctuating CpG methylation as a lineage marker to track stem cell clonal dynamics of hematopoiesis. We show, via the shared prenatal circulation of monozygotic twins, that weak selection conferred by stem cell variation created before birth can reliably yield clonal hematopoiesis later in life. Theory indicates weak selection will lead to dominance given enough time and large enough population sizes. Human hematopoiesis satisfies both these conditions. Stochastic loss of weakly selected variants is naturally prevented by the expansion of stem cell lineages during development. The dominance of stem cell clones created before birth is supported by blood fluctuating CpG methylation patterns that exhibit low correlation between unrelated individuals but are highly correlated between many elderly monozygotic twins. Therefore, clonal hematopoiesis driven by weak selection in later life appears to reflect variation created before birth. Clonal hematopoiesis becomes increasingly common with age. Here the authors track stem cell dynamics in monozygotic twins and provide evidence that clonal hematopoiesis in later life reflects weak selection conferred by stem cell variation before birth. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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