The self-renewing lymphoid-biased hematopoietic stem cells support long-term lymphopoiesis in mice
Lymphopoiesis is profoundly impaired during ageing largely due to ageing-susceptible changes of hematopoietic stem cells (HSCs). How to maximize the preservation of lymphopoiesis during ageing remains unknown and whether there exists a specific population with life-long lymphoid potential not intensively affected by ageing is of substantial scientific and translational significance. Here, we…
Lymphopoiesis, the process of producing immune cells, declines with age due to changes in hematopoietic stem cells (HSCs). However, scientists have discovered a unique subset of HSCs that may help preserve lymphoid potential throughout a lifetime. These self-renewing, lymphoid-biased hematopoietic stem cells (Ly-biased HSCs) are found within the EPCR+CD150-CD48-LSK (HSC2) population, which is designated as EPCR+MPP6 (CD34-CD135-HSC2).
Recent research has shown that these cells maintain their ability to differentiate into various blood cell types even in older mice, just like regular HSCs. Moreover, they continue to contribute to a balanced immune system as aging progresses. This discovery is supported by molecular and cellular evidence at both the genetic and protein levels.
Crucially, EPCR+MPP6 and HSCs rarely transform into each other during cell division and during normal functioning in the body, suggesting they may originate from separate pathways. This finding implies that Ly-biased HSCs could serve as a vital reserve population to support immune function, offering new avenues for research and potential treatments to combat age-related immune decline.
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