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

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

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

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.

Diversity in the oligodendrocyte lineage: Plasticity or heterogeneity?

Heterogeneity is a widely recognized phenomenon within the majority of cell types in the body including cells of the central nervous system (CNS). The heterogeneity of neurons based on their distinct transmission modes and firing patterns has been recognized for decades, and is necessary to coordinate the immense variety of functions of the CNS. More recently, heterogeneity in glial cells has been identified, including heterogeneity in oligodendrocyte progenitor cells (OPCs) and oligodendrocytes. OPC subpopulations have been described based on their developmental origin, anatomical location in the grey or white matter, and expression of surface receptors. Oligodendrocytes are categorised according to differences in gene expression, myelinogenic potential, and axon specificity. Much of what is described as heterogeneity in oligodendrocyte lineage cells (OLCs) is based on phenotypic differences. However, without evidence for functional differences between putative subgroups of OLCs, distinguishing heterogeneity from plasticity and lineage state is difficult. Identifying functional differences between phenotypically distinct groups are therefore necessary for a deeper understanding of the role of OLCs in health and disease.

Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists.

BACKGROUND: Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/no), seizure type, consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics (percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their interpretation. RESULTS: Only a fair level of agreement (κ = 0.40) was found for epileptic seizure presence. Overall agreement of seizure type was moderate (κ = 0.44), with primary generalised seizures showing the highest level of agreement (κ = 0.60), and focal the lowest (κ =0.31). Fair agreement was found for consciousness status and the presence of autonomic signs (κ = 0.21-0.40), but poor agreement for neurobehavioral signs (κ = 0.16). Agreement for motor signs ranged from poor (κ = ≤ 0.20) to moderate (κ = 0.41-0.60). Differences between specialists and non-specialists were identified. CONCLUSIONS: The relatively low levels of agreement described here highlight the need for further discussions between neurology experts regarding classifying and describing epileptic seizures, and additional training of non-specialists to facilitate accurate diagnosis. There is a need for diagnostic tools (e.g. electroencephalogram) able to differentiate between epileptic and non-epileptic paroxysms.

Getting on with a PhD in a changing political landscape.

Myfanwy Hill wrote this on June 24, just after the result of the EU referendum was announced. Almost exactly a year after she started her PhD in Cambridge, she reflects on how far she has come and where she is going.

Challenges of a PhD.

While Myfanwy Hill's PhD studies pose an 'enjoyable challenge', she has found that learning to manage her time and studies requires a new level of self discipline.

Ups and downs of life as a PhD student.

Myfanwy Hill reflects on her coping strategies and recognises her limitations. She has learnt why it is important to relax and recharge.