The blood remembers: HSC-iM and the cancer continuum

Three long-standing observations- the persistence of haematological perturbations after severe infection, the acceleration of biological ageing by chronic inflammatory disorders, and the preferential expansion of clonal haematopoiesis (CH) in older or inflamed individuals- have long suggested that the haematopoietic stem cell (HSC) compartment must retain a cellular record of past insults. The demonstration that human HSCs retain inflammatory memory may represent a conceptual shift comparable to the discovery of clonal haematopoiesis itself, providing a mechanistic framework linking infection history, ageing, and cancer evolution. In mice, the molecular nature of this record has been gradually delineated over the past decade [ 1 , 2 ]. In humans, however, the evidence has been almost entirely indirect. The recent study by Zeng and colleagues closes much of this gap by combining xenograft inflammation–recovery models with single-cell multiomic profiling, and by triangulating the resulting xenograft-derived signatures with patient cohorts representing severe COVID-19, sickle cell disease (SCD), physiological ageing, and CH [ 3 ].