How are haematopoietic stem cells (HSCs) protected from inflammation, which increases with age and can deplete HSCs? Adiponectin, an anti-inflammatory factor that is not required for HSC function or haematopoiesis, promotes stem/progenitor cell proliferation after bacterial infection and myeloablation. Adiponectin binds two receptors, AdipoR1 and AdipoR2, which have ceramidase activity that increases upon adiponectin binding. Here we found that adiponectin receptors are non-cell-autonomously required in haematopoietic cells to promote HSC quiescence and self-renewal.
View Article and Find Full Text PDFMetabolism has been studied mainly in cultured cells or at the level of whole tissues or whole organisms in vivo. Consequently, our understanding of metabolic heterogeneity among cells within tissues is limited, particularly when it comes to rare cells with biologically distinct properties, such as stem cells. Stem cell function, tissue regeneration and cancer suppression are all metabolically regulated, although it is not yet clear whether there are metabolic mechanisms unique to stem cells that regulate their activity and function.
View Article and Find Full Text PDFThe activation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle coordinates systemic metabolic responses to exercise. Autophagy-a lysosomal degradation pathway that maintains cellular homeostasis-is upregulated during exercise, and a core autophagy protein, beclin 1, is required for AMPK activation in skeletal muscle. Here we describe a role for the innate immune-sensing molecule Toll-like receptor 9 (TLR9), and its interaction with beclin 1, in exercise-induced activation of AMPK in skeletal muscle.
View Article and Find Full Text PDFTo facilitate reference-material selection for clinical genetic testing laboratories, we developed VarCover, open-source software hosted on GitHub, which accepts a file of variants and returns an approximately minimum set (min-set) of samples covering the targeted alleles. VarCover employs the SetCoverPy package, sample weights, and preselection of singleton-possessing samples to efficiently solve the min-set cover problem. As a test case, we attempted to find a min-set of reference samples from the 1000 Genomes Project to cover 237 variants considered putatively pathogenic (of which 12 were classified as pathogenic or likely pathogenic) in the original 56 medically actionable genes recommended by the American College of Medical Genetics and Genomics (ACMG).
View Article and Find Full Text PDFThis article shows an example of the peer review process for "Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal" (Xie et al., 2019).
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