AI Article Synopsis
- Hematopoiesis is the process where our body makes different types of blood cells from special cells called multipotent hematopoietic stem cells (HSC).
- Researchers studied how changes in certain genes, like KRAS and RasGRP1, affect these blood cells and found that these changes can cause an imbalance, making more of some types of blood cells than others.
- They discovered that RasGRP1 helps keep some stem cells in a resting state, while KRAS reduces these resting cells, showing how different genes can change how our blood cells develop.
Article Abstract
Normal hematopoiesis requires constant prolific production of different blood cell lineages by multipotent hematopoietic stem cells (HSC). Stem- and progenitor- cells need to balance dormancy with proliferation. How genetic alterations impact frequency, lineage potential, and metabolism of HSC is largely unknown. Here, we compared induced expression of KRAS or RasGRP1 to normal hematopoiesis. At low-resolution, both Ras pathway lesions result in skewing towards myeloid lineages. Single-cell resolution CyTOF proteomics unmasked an expansion of HSC- and progenitor- compartments for RasGRP1, contrasted by a depletion for KRAS . SCENITH™ quantitates protein synthesis with single-cell precision and corroborated that immature cells display low metabolic SCENITH™ rates. Both RasGRP1 and KRAS elevated mean SCENITH™ signals in immature cells. However, RasGRP1-overexpressing stem cells retain a metabolically quiescent cell-fraction, whereas this fraction diminishes for KRAS . Our temporal single cell proteomics and metabolomics datasets provide a resource of mechanistic insights into altered hematopoiesis at single cell resolution.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769276 | PMC |
| http://dx.doi.org/10.1101/2023.12.20.572584 | DOI Listing |
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