期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 213, 期 11, 页码 2259-2267出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20160168
关键词
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资金
- National Institutes of Health [P30 AG038070, T32 HD007065]
- Ellison Medical Foundation [AG-NS-0993-13]
- Pyewacket Fund
Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of changes with age in the heterogeneous multipotent progenitor (MPP) cell compartment, which is long lived and responsible for dynamically regulating output of mature hematopoietic cells. In this study, we observe an early and progressive loss of lymphoid-primed MPP cells (LMPP/MPP4) with aging, concomitant with expansion of HSCs. Transcriptome and in vitro functional analyses at the single-cell level reveal a concurrent increase in cycling of aging LMPP/MPP4 with loss of lymphoid priming and differentiation potential. Impaired lymphoid differentiation potential of aged LMPP/MPP4 is not rescued by transplantation into a young bone marrow microenvironment, demonstrating cell-autonomous changes in the MPP compartment with aging. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging.
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