Cellular aging leads to functional heterogeneity of hematopoietic stem cells: a modeling perspective.

摘要: Summary Hematopoietic stem cells (HSCs) are the source for life-long supply of functional in peripheral blood while they simultaneously maintain their own reserve pool. However, there is accumulating evidence that HSCs themselves subject to quantitative and qualitative exhaustion. Although several processes linked mitotic activity can potentially account observed aging phenomena (e.g., DNA damage, telomere shortening, epigenetic modification), a precise understanding HSC exhaustion still missing. It particularly unclear how individual on single-cell level translate phenotypic overall tissue whether implication an age-structured population. We address these issues by applying novel mathematical model organization which division-specific, cumulative alterations cell quality determine appearance Adapting number basic experimental findings, we quantify additional heterogeneity introduced population individually cells. Based this model, able conclude division-dependent cellular explain wide range needs be considered as highly heterogeneous process. furthermore report between young old appears closely similar described long- short-term repopulating speculate differential, division-coupled introduces intra-animal variability also accounts with respect repopulation ability HSCs.