9 research outputs found

    Niche stiffness underlies the ageing of central nervous system progenitor cells.

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    Ageing causes a decline in tissue regeneration owing to a loss of function of adult stem cell and progenitor cell populations1. One example is the deterioration of the regenerative capacity of the widespread and abundant population of central nervous system (CNS) multipotent stem cells known as oligodendrocyte progenitor cells (OPCs)2. A relatively overlooked potential source of this loss of function is the stem cell 'niche'-a set of cell-extrinsic cues that include chemical and mechanical signals3,4. Here we show that the OPC microenvironment stiffens with age, and that this mechanical change is sufficient to cause age-related loss of function of OPCs. Using biological and synthetic scaffolds to mimic the stiffness of young brains, we find that isolated aged OPCs cultured on these scaffolds are molecularly and functionally rejuvenated. When we disrupt mechanical signalling, the proliferation and differentiation rates of OPCs are increased. We identify the mechanoresponsive ion channel PIEZO1 as a key mediator of OPC mechanical signalling. Inhibiting PIEZO1 overrides mechanical signals in vivo and allows OPCs to maintain activity in the ageing CNS. We also show that PIEZO1 is important in regulating cell number during CNS development. Thus we show that tissue stiffness is a crucial regulator of ageing in OPCs, and provide insights into how the function of adult stem and progenitor cells changes with age. Our findings could be important not only for the development of regenerative therapies, but also for understanding the ageing process itself.The work was supported by European Research Council (ERC) grant 772798 (to K.J.C.) and 772426 (to K.F.); the UK Multiple Sclerosis Society (to R.J.M.F.); Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/M008827/1 (to K.J.C and R.J.M.F.) and BB/N006402/1 (to K.F.); the Adelson Medical Research Foundation (R.J.M.F. and D.H.R.); an EMBO Long-Term Fellowship ALTF 1263-2015 and European Commission FP7 actions LTFCOFUND2013, GA-2013-609409 (to I.P.W.); and a core support grant from the Wellcome Trust and Medical Research Council (MRC) to the Wellcome Trust–MRC Cambridge Stem Cell Institute

    Stratigrafiska undersökningar i sjön Vuolep Njakajaure, Abisko

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    Summary: This is a studie of Holocene lake sediments. The investigated lake, Vuolep Njakajaure (68°20'N, 18°47'O) is situated in the Abisko valley in the northern parts of the Caledonides. In this study four marginal cores of nonlaminated algalgyttja have been studied with respect to magnetic concentration parameters (ie susceptibility(χ) and SIRM) and loss on ignition. Core correlations have been carried out based on SIRM/χ and S-ratio. The core correlations indicates a hiatus at the beginning of Holocene in two of the cores. One core was selected as a main core. This main core was analysed with respect to pollen composition and indirectly 14C-dated by correlation to Sonesson (1968). Thus the sedimentation-rates were calculated in all of the cores. Snowball (1993) has shown that the S-ratio can be an indicator to climatic changes, because dissolution of magnetitegrains is greater compared to hematite-grains during warmer periods. S-ratio and SIRM/χ where compared to the climatic changes, as described by the pollenzonation, in the main core to investigate if they reflect climatic changes. In the upper part of the main core a correlation of the climatic changes and the mineral magnetic parameters was found. This is a strong indicator to high representativity of climatic changes, because two independent parameters ie pollen and magnetics correlates.Populärvetenskaplig sammanfattning: Detta är en studie av Holocena sjösediment. Den undersökta sjön, Vuolep Njakajaure (68°20'N, 18°47'O) ligger i Abiskodalen i de norra delarna av Kaledoniderna. I denna studie har fyra borrkärnor av alggyttja jämförts med magnetiska analyser (susceptibilitet(χ), SIRM) och glödförlust. Borrkärnorna har korrelerats i huvudsak baserat på SIRM/χ och S-kvot. Korreleringarna indikerar en hiatus i början av Holocen i två av borrkärnorna. En av borrkärnorna valdes till huvudborrkärna och i den analyserades pollensammansättningen. Huvudborrkärnan 14C-daterades indirekt genom korrelering till Sonesson (1968). Därefter beräknades sedimentationshastigheter i alla borrkärnorna. Snowball (1993) har visat att S-kvoten kan vara en klimatindikator genom att magnetit upplöses i större utsträckning än hematit under varmare perioder. S-kvot och SIRM/χ jämfördes med klimatförändringar, så som pollenzoneringen beskriver dem, i huvudborrkärnan för att undersöka om de återspeglar klimatförändringar. I den övre delen av huvudborrkärnan finns ett samband mellan klimatförändringar och magnetmineralogin. Detta är en stark indikation på god representativitet för klimatförändringar pga överensstämmelse mellan två oberoende parametrar
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