Single Novel single cell assay reveals progressive lymphoid defect in aging multipotent hematopoietic progenitors cell RNA-seq reveals LMPP clonal dynamics in aging.

Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of the dynamic changes with age in the heterogeneous multipotent hematopoietic progenitor cell compartment, which regulates output of differentiated lymphoid cells. In this study, we observed progressive and specific loss of lymphoid-primed multipotent progenitor cells (LMPP/MPP4) as young animals began to age. Single cell RNA-seq revealed a concomitant increase in cycling of these progenitors with loss of a lymphoid priming signature. To interrogate functional multipotency of single cells, we developed a novel, feeder-free in vitro assay to concurrently assess lymphoid and myeloid potential. This assay revealed altered clonal composition of the LMPP/MPP4 compartment with aging, where progenitors with B cell and macrophage-restricted potential are lost while functionally multipotent progenitors are preserved. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging. Overall design: Examination of single cell RNA-seq transcriptomes in LMPP isolated from the bone marrow of 4mo and 14mo wild-type C57BL/6J female mice

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Young K, Borikar S, Bell R, Kuffler L, Philip V, Trowbridge JJ