How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, Eed, in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications. Notably, H3K9me3 was lost at these PRC2 targets before gene activation. Neuronal survival was not compromised; instead, there was a reduction in subtype-specific gene expression and a progressive impairment of dopaminergic and serotonergic neuronal function, leading to behavioral deficits characteristic of Parkinson's disease and anxiety. Single-cell analysis revealed subtype-specific vulnerability to loss of PRC2 repression in dopamine neurons of the substantia nigra. Our study reveals that a PRC2-dependent nonpermissive chromatin state is essential to maintain the subtype identity and function of dopaminergic and serotonergic neurons.

Deep metabarcoding offers an efficient and reproducible approach to biodiversity monitoring, but noisy data and incomplete reference databases challenge accurate diversity estimation and taxonomic annotation. Here, we introduce a novel algorithm, NEEAT, for removing spurious operational taxonomic units (OTUs) originating from nuclear-embedded mitochondrial DNA sequences (NUMTs) or sequencing errors. It integrates 'echo' signals across samples with the identification of unusual evolutionary patterns among similar DNA sequences. We also extensively benchmark current tools for chimera removal, taxonomic annotation and OTU clustering of deep metabarcoding data. The best performing tools/parameter settings are integrated into HAPP, a high-accuracy pipeline for processing deep metabarcoding data. Tests using CO1 data from BOLD and large-scale metabarcoding data on insects demonstrate that HAPP significantly outperforms existing methods, while enabling efficient analysis of extensive datasets by parallelizing computations across taxonomic groups.

Psoriasis is a common chronic inflammatory skin disease determined by genetic and environmental factors, resulting in the activation of IL-23/IL-17-mediated immune response, epidermal hyperproliferation, and keratinocyte activation. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts > 500 nucleotides with diverse regulatory functions; their role in epidermal dysfunction in psoriasis is poorly understood. To identify epidermal transcripts with potential roles in psoriasis, including lncRNAs, we performed RNA sequencing on keratinocytes from psoriasis and healthy skin. We identified 889 differentially expressed lncRNAs, many of which with yet unknown functions. RP11-295G20.2 was identified as a lncRNA significantly induced in psoriasis keratinocytes, and this was verified by qRT-PCR and by single-molecule in situ hybridisation. Analysis of subcellular fractions of epidermis revealed a cytoplasmic localisation in line with results of single molecule in situ hybridisation. We report that RP11-295G20.2 has a skin-enriched expression, and within skin it is mainly expressed in suprabasal epidermal layers. Moreover, RP11-295G20.2 is induced by the key psoriasis cytokine IL-17A and shows a dynamic regulation during keratinocyte differentiation with upregulation during early differentiation and downregulation in the late stage. Knockdown of RP11-295G20.2 in keratinocytes promotes terminal differentiation. Based on our findings, we named RP11-295G20.2 Cytoplasmic Differentiation-Associated Epidermal RNA, CYDAER. In summary, our study provides a comprehensive characterisation of the non-coding RNA landscape of psoriasis keratinocytes and identifies CYDAER as a skin-enriched lncRNA regulating keratinocyte differentiation. Our data suggest that overexpression of CYDAER may contribute to altered differentiation in psoriatic epidermis.

Spinal cord ependymal cells display neural stem cell properties in vitro and generate scar-forming astrocytes and remyelinating oligodendrocytes after injury. We report that ependymal cells are functionally heterogeneous and identify a small subpopulation (8% of ependymal cells and 0.1% of all cells in a spinal cord segment), which we denote ependymal A (EpA) cells, that accounts for the in vitro stem cell potential in the adult spinal cord. After spinal cord injury, EpA cells undergo self-renewing cell division as they give rise to differentiated progeny. Single-cell transcriptome analysis revealed a loss of ependymal cell gene expression programs as EpA cells gained signaling entropy and dedifferentiated to a stem-cell-like transcriptional state after an injury. We conclude that EpA cells are highly differentiated cells that can revert to a stem cell state and constitute a therapeutic target for spinal cord repair.

Heterotrophic bacteria are important drivers of nitrogen (N) cycling and the processing of dissolved organic matter (DOM). Projected increases in precipitation will potentially cause increased loads of riverine DOM to the Baltic Sea and likely affect the composition and function of bacterioplankton communities. To investigate this, the effects of riverine DOM from two different catchment areas (agricultural and forest) on natural bacterioplankton assemblages from two contrasting sites in the Baltic Sea were examined. Two microcosm experiments were carried out, where the community composition (16S rRNA gene sequencing), the composition of a suite of N-cycling genes (metagenomics) and the abundance and transcription of ammonia monooxygenase (amoA) genes involved in nitrification (quantitative PCR) were investigated. The river water treatments evoked a significant response in bacterial growth, but the effects on overall community composition and the representation of N-cycling genes were limited. Instead, treatment effects were reflected in the prevalence of specific taxonomic families, specific N-related functions and in the transcription of amoA genes. The study suggests that bacterioplankton responses to changes in the DOM pool are constrained to part of the bacterial community, whereas most taxa remain relatively unaffected.

The study of parallel ecological divergence provides important clues to the operation of natural selection. Parallel divergence often occurs in heterogeneous environments with different kinds of environmental gradients in different locations, but the genomic basis underlying this process is unknown. We investigated the genomics of rapid parallel adaptation in the marine snail Littorina saxatilis in response to two independent environmental axes (crab-predation versus wave-action and low-shore versus high-shore). Using pooled whole-genome resequencing, we show that sharing of genomic regions of high differentiation between environments is generally low but increases at smaller spatial scales. We identify different shared genomic regions of divergence for each environmental axis and show that most of these regions overlap with candidate chromosomal inversions. Several inversion regions are divergent and polymorphic across many localities. We argue that chromosomal inversions could store shared variation that fuels rapid parallel adaptation to heterogeneous environments, possibly as balanced polymorphism shared by adaptive gene flow.

The sympatric existence of genetically distinguishable populations of the same species remains a puzzle in ecology. Coexisting salmonid fish populations are known from over 100 freshwater lakes. Most studies of sympatric populations have used limited numbers of genetic markers making it unclear if genetic divergence involves certain parts of the genome. We returned to the first reported case of salmonid sympatry, initially detected through contrasting homozygosity at a single allozyme locus (coding for lactate dehydrogenase A) in brown trout in the small Lakes Bunnersjöarna, Sweden. First, we verified the existence of the two coexisting demes using a 96-SNP fluidigm array. We then applied whole-genome resequencing of pooled DNA to explore genome-wide diversity within and between these demes; nucleotide diversity was higher in deme I than in deme II. Strong genetic divergence is observed with genome-wide FST ≈ 0.2. Compared with data from populations of similar small lakes, this divergence is of similar magnitude as that between reproductively isolated populations. Individual whole-genome resequencing of two individuals per deme suggests higher inbreeding in deme II versus deme I, indicating different degree of isolation. We located two gene-copies for LDH-A and found divergence between demes in a regulatory section of one of these genes. However, we did not find a perfect fit between the sequence data and previous allozyme results, and this will require further research. Our data demonstrates genome-wide divergence governed mostly by genetic drift but also by diversifying selection in coexisting populations. This type of hidden biodiversity needs consideration in conservation management.