| Autor: |
Zhonghe Ke, James DeGregori, Jason R. Myers, Robert S. Welner, Eric M. Pietras, Rachel L Gessner, Kelly C. Higa, Dirk Loeffler, Craig T. Jordan, Hideaki Nakajima, Beau M Idler, Taylor S. Mills, Jennifer L. Rabe, Giovanny Hernandez, Nouraiz Ahmed, John M. Ashton, Brett M. Stevens, James S. Chavez, Timm Schroeder, Hyunmin Kim |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.1101/2020.05.18.102830 |
| Popis: |
SummaryLoss of hematopoietic stem cell (HSC) quiescence and resulting clonal expansion are common initiating events in the development of hematological malignancy. Likewise, chronic inflammation related to aging, disease and/or tissue damage is associated with leukemia progression, though its role in oncogenesis is not clearly defined. Here, we show that PU.1-dependent repression of protein synthesis and cell cycle genes in HSC enforces homeostatic protein synthesis levels and HSC quiescence in response to IL-1 stimulation. These genes are constitutively de-repressed in PU.1-deficient HSC, leading to activation of protein synthesis, loss of quiescence and aberrant expansion of HSC. Taken together, our data identify a mechanism whereby HSC regulate their cell cycle activity and pool size in response to chronic inflammatory stress. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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