Fatty acid oxidation is of uncertain importance in most stem cells. We show by C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes. CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice.
View Article and Find Full Text PDFDuring persistent antigen stimulation, exhausted CD8 T cells are continuously replenished by self-renewing stem-like T cells. However, how CD8 T cells adapt to chronic stimulation remains unclear. Here, we show that persistent antigen stimulation primes chromatin for regulation by the redox-sensing KEAP1-NRF2 pathway.
View Article and Find Full Text PDFAscorbate (vitamin C) limits hematopoietic stem cell (HSC) function and suppresses leukemia development by promoting the function of the Tet2 tumor suppressor. In humans, ascorbate is obtained from the diet while in mice it is synthesized in the liver. In this study, we show that deletion of the Slc23a2 ascorbate transporter severely depleted ascorbate from hematopoietic cells.
View Article and Find Full Text PDFThere exists extensive variation in eye size. Much work has provided a connection between light availability and differences in eye size across taxa. Experimental tests of the role of the light environment on the evolution of eye size are lacking.
View Article and Find Full Text PDFUnlabelled: Despite being the leading cause of cancer deaths, metastasis remains a poorly understood process. To identify novel regulators of metastasis in melanoma, we performed a large-scale RNA sequencing screen of 48 samples from patient-derived xenograft (PDX) subcutaneous melanomas and their associated metastases. In comparison with primary tumors, expression of glycolytic genes was frequently decreased in metastases, whereas expression of some tricarboxylic acid (TCA) cycle genes was increased in metastases.
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