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Sökning: WFRF:(Wigge C)

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  • Henriksen, T. I., et al. (författare)
  • Dysregulated autophagy in muscle precursor cells from humans with type 2 diabetes
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Autophagy is active during cellular remodeling including muscle differentiation. Muscle differentiation is dysregulated in type 2 diabetes and we therefore hypothesize that muscle precursor cells from people with type 2 diabetes (T2DM) have a dysregulation of their autophagy leading to impaired myogenesis. Muscle precursor cells were isolated from people with T2DM or healthy controls and differentiated in vitro. Autophagy marker levels were assessed by immunoblotting. Differentially expressed autophagy-related genes between healthy and T2DM groups were identified based on a previously published RNA-sequencing data-set, which we verified by RT-qPCR. siRNA was used to assess the function of differentially expressed autophagy genes. Basal autophagy increases during human muscle differentiation, while T2DM muscle cells have reduced levels of autophagy marker ATG7 and show a blunted response to starvation. Moreover, we demonstrate that the 3 non-canonical autophagy genes DRAM1, VAMP8 and TP53INP1 as differentially expressed between healthy and T2DM groups during myoblast differentiation, and that T53INP1 knock-down alters expression of both pro-and anti-apoptotic genes. In vitro differentiated T2DM muscle cells show differential expression of autophagy-related genes. These genes do not regulate myogenic transcription factors but may rather be involved in p53-associated myoblast apoptosis during early myogenesis.
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3.
  • Mazzurana, Luca, et al. (författare)
  • Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
  • 2021
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:5, s. 554-568
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
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