Multimodal omics identifies a lymphoid-biased multipotent progenitor population with limited age-associated remodeling.

Young MPP6 in mice is an HSC-like, lymphoid-biased progenitor with long-term reconstitution capacity, low chromatin accessibility, and low metabolic activity.

• Why it matters: Hematopoietic aging shifts output from lymphoid to myeloid, but it is unclear whether remodeling affects all HSPCs uniformly or selectively targets specific progenitor populations.
• What they did: The study profiled HSCs and MPP1-6 from young versus aged mice using transcriptomic, epigenomic, metabolomic, and lipidomic layers plus single-cell division and serial transplantation assays.
• The result: Aging preserved long-term lymphoid reconstitution in MPP6 with limited transcriptional/regulatory remodeling, while most HSPCs—especially HSCs—showed myeloid-biased expansion, extensive distal regulatory changes, and oxidative-stress-linked long-chain polyunsaturated phospholipid accumulation.

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