Project description:Cell size is tightly controlled in healthy tissues, but it is unclear how deviations in cell size affect cell physiology. To address this, we measured how the proteome changes with cell size. Protein concentration changes are widespread and predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA damage-, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by an increase in ploidy. Together, our findings show how cell size could impact many aspects of cell physiology through remodeling the proteome and provide a rationale for cell size control and polyploidization.
Project description:Stem cells are remarkably small in size. Human hematopoietic stem cells (HSCs) measure a mere 7 μm in diameter. Whether small size is important for stem cell function is unknown. We find that murine HSCs enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferative potential. We further show that preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing the size of large HSCs by shortening G1 averts the loss of stem cell potential. Naturally large HSCs also exhibit decreased stem cell potential indicating that large size characterizes exhausted HSCs under physiological conditions. Finally, we show that our findings are relevant to aging. A fraction of murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function and propose that stem cell enlargement contributes to their functional decline during aging.
Project description:A parental immortalized mouse keratinocyte cell line which lacks integrin α3β1 and α9β1 were engineered to express either α3β1, α9β1, or α3β1 and α9β1 in combination. The conditioned medium from these cell lines were analyzed by MS/MS.
Project description:Transgenic rice plants expressing the Arabidopsis phloem-specific sucrose transporter AtSUC2, which loads Suc into the phloem, showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. The goal was to reveal how expressed AtSUC2 in rice leads to increased grain yield analyzing global gene expression.
Project description:Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses we find that 11-days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition, increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.
Project description:We and other groups doumented that astrocytes modulate migration, maturation and myelin sythesis of oligodendrocytes through release of neurotransmitters, cytokins and other signaling molecules. However, much less is known about on how the oligodendrocytes affects the astrocytes. We compared the transcriptome of cortical astrocytes when cultured alone and co-cultured with non-touching immortalized precursor oligodendrocytes (Oli-neu) in insert systems. Experimental data indicate that the oligodendrocyte-conditioning medium has a substantial effect on the the gene expression in astrocytes. Moreover, oligodendendrocyte proximity remodels major astrocyte functional pathways.