Journal
CELL REPORTS
Volume 25, Issue 11, Pages 2992-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.11.056
Keywords
-
Categories
Funding
- Sackler Foundation
- Howard Hughes Medical Institute
- Klaman Cell Observatory at the Broad Institute
- Human Frontiers Science Foundation
- National Research Service Award [CA183220]
- UCLA/Caltech Medical Scientist Training Program
- Canadian Institutes for Health Research
- Charles A. King Trust Postdoctoral Research Fellowship Program
- Bank of America, N.A.
- Simeon J. Fortin Charitable Foundation
Ask authors/readers for more resources
Long-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. However, with age, the balance is disrupted, and LT-HSCs produce a myeloid-biased output, resulting in poor immune responses to infectious challenge and the development of myeloid leukemias. Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. Using single-cell RNA sequencing (scRNA-seq), we identify a myeloid-biased subset within the LT-HSC population (mLT-HSCs) that is prevalent among aged LT-HSCs. We identify CD61 as a marker of mLT-HSCs and show that CD61-high LT-HSCs are uniquely primed to respond to acute inflammatory challenge. We predict that several transcription factors regulate the mLT-HSCs gene program and show that Klf5, Ikzf1, and Stat3 play an important role in age-related inflammatory myeloid bias. We have therefore identified and isolated an LT-HSC subset that regulates myeloid versus lymphoid balance under inflammatory challenge and with age.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available