Whole exome sequencing of aged murine bone marrow hematopoietic cells

Aging generally predisposes stem cells to functional decline. Here, we report that hematopoietic stem cells (HSCs) acquire metabolic resilience that promotes cell survival, increasing their cell numbers with age. Little is known about whether aged murine HSCs undergo clonal expansion similarly to human hematopoiesis. Here we performed whole exome sequencing of aged bone marrow cells to investigate whether there is clonal expansion with specific genetic alterations, and if it is the case, there are commonly mutated genes associated with human clonal hematopoiesis. We found that there are no commonly mutated genes observed in human clonal hematopoisis, and thus concluded that HSC expansion in murine HSCs is a process apart from clonal expansion caused by specific genetic alterations.

衰老通常会使干细胞更易发生功能衰退。本研究发现，造血干细胞（hematopoietic stem cells，HSCs）会获得代谢韧性以促进细胞存活，并随衰老进程增加自身细胞数量。目前学界对于衰老小鼠的造血干细胞是否会如同人类造血系统一样发生克隆扩增仍知之甚少。为此，我们对衰老小鼠的骨髓细胞进行了全外显子组测序，以探究衰老小鼠造血干细胞是否会伴随特定遗传变异发生克隆扩增；若确实存在此类扩增，则需明确是否存在与人类克隆性造血相关的常见突变基因。我们发现，与人类克隆性造血相关的常见突变基因在本研究的小鼠样本中并未被观测到，因此我们得出结论：小鼠造血干细胞的扩增过程，并非由特定遗传变异驱动的克隆扩增过程。