The self-renewing lymphoid-biased hematopoietic stem cells support long-term lymphopoiesis in mice

EPCR+MPP6 (CD34-CD135-HSC2) Ly-biased hematopoietic stem cells in mice preserve lymphoid-biased reconstitution during ageing, maintaining similar lymphoid potential to HSCs in young animals.

• Why it matters: Ageing impairs lymphopoiesis, largely through changes in hematopoietic stem cells, but it is unclear how to preserve lymphoid output or whether a lifelong lymphoid-leaning HSC subset resists ageing.
• What they did: The authors identified EPCR+MPP6 within EPCR+CD150-CD48-LSK (HSC2), then compared multi-lineage and lymphoid-biased reconstitution in young versus aged mice and validated lymphoid programs by transcriptome and proteomics.
• The result: EPCR+MPP6 and HSCs rarely generated one another after the first division in vitro and under homeostasis in vivo, implying an earlier lymphoid bifurcation and a backup source for age-related lymphopoiesis.

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