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Cabezas-Wallscheid, Nina; Buettner, Florian; Sommerkamp, Pia; Klimmeck, Daniel; Ladel, Luisa; Thalheimer, Frederic B.; Pastor-Flores, Daniel; Roma, Leticia P.; Renders, Simon; Zeisberger, Petra; Przybylla, Adriana; Schönberger, Katharina; Scognamiglio, Roberta; Altamura, Sandro; Florian, Carolina M.; Fawaz, Malak; Vonficht, Dominik; Tesio, Melania; Collier, Paul; Pavlinic, Dinko; Geiger, Hartmut; Schroeder, Timm; Benes, Vladimir; Dick, Tobias P.; Rieger, Michael A.; Stegle, Oliver; Trumpp, Andreas
Cell, 05/2017, Letnik: 169, Številka: 5Journal Article
Dormant hematopoietic stem cells (dHSCs) are atop the hematopoietic hierarchy. The molecular identity of dHSCs and the mechanisms regulating their maintenance or exit from dormancy remain uncertain. Here, we use single-cell RNA sequencing (RNA-seq) analysis to show that the transition from dormancy toward cell-cycle entry is a continuous developmental path associated with upregulation of biosynthetic processes rather than a stepwise progression. In addition, low Myc levels and high expression of a retinoic acid program are characteristic for dHSCs. To follow the behavior of dHSCs in situ, a Gprc5c-controlled reporter mouse was established. Treatment with all-trans retinoic acid antagonizes stress-induced activation of dHSCs by restricting protein translation and levels of reactive oxygen species (ROS) and Myc. Mice maintained on a vitamin A-free diet lose HSCs and show a disrupted re-entry into dormancy after exposure to inflammatory stress stimuli. Our results highlight the impact of dietary vitamin A on the regulation of cell-cycle-mediated stem cell plasticity. Display omitted Display omitted •Continuous increase of biosynthesis during transition from dormant to active HSCs•Gprc5c-EGFP reporter mice allow identification and isolation of dormant HSCs•Retinoic acid-vitamin A regulates HSC plasticity during stress-mediated activation•Vitamin A-deficient diet impairs the HSC compartment in mice Metabolic inputs control the entry and exit of hematopoietic stem cells from dormancy and suggest the potential application of vitamin A in hematopoietic disorders and leukemias.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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