Dataset Information

Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age.

ABSTRACT: 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.

SUBMITTER: Mann M

PROVIDER: S-EPMC6424521 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age.

Mann Mati M Mehta Arnav A de Boer Carl G CG Kowalczyk Monika S MS Lee Kevin K Haldeman Pearce P Rogel Noga N Knecht Abigail R AR Farouq Daneyal D Regev Aviv A Baltimore David D

Cell reports 20181201 11

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 sequencin ...[more]

PMID: 30540934

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Dataset Information

Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age.

Publications

Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age.

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