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Journal of Autoimmunity Jun 2024Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two...
Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two independent SLE patient cohorts by three machine learning models revealed the pseudogene UHRF1P as a novel SLE biomarker. The pseudogene-encoded UHRF1P protein was overexpressed in peripheral blood T cells of SLE patients. The UHRF1P protein lacks the amino-terminus of its parental UHRF1 protein, resulting in missing the proteasome-binding ubiquitin-like (Ubl) domain of UHRF1. T-cell-specific UHRF1P transgenic mice manifested the induction of IL-17A and autoimmune inflammation. Mechanistically, UHFR1P prevented UHRF1-induced Lys48-linked ubiquitination and degradation of MAP4K3 (GLK), which is a kinase known to induce IL-17A. Consistently, IL-17A induction and autoimmune phenotypes of UHRF1P transgenic mice were obliterated by MAP4K3 knockout. Collectively, UHRF1P overexpression in T cells inhibits the E3 ligase function of its parental UHRF1 and induces autoimmune diseases.
Topics: Lupus Erythematosus, Systemic; Animals; Interleukin-17; Ubiquitin-Protein Ligases; Humans; Mice; CCAAT-Enhancer-Binding Proteins; Mice, Transgenic; Protein Serine-Threonine Kinases; Ubiquitination; Mice, Knockout; Disease Models, Animal; Signal Transduction; T-Lymphocytes; Autoimmunity; Female
PubMed: 38643728
DOI: 10.1016/j.jaut.2024.103221 -
Communications Biology Apr 2024Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform...
Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). scTCRseq and integration with scRNA data have not been demonstrated on companion dogs with cancer. Here, five healthy dogs, two dogs with T cell lymphoma and four dogs with melanoma are selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. Single-cell suspensions of PBMCs or lymph node aspirates are profiled using scRNA and dog-specific scTCRseq primers. In total, 77,809 V(D)J-expressing cells are detected, with an average of 3498 (348 - 5,971) unique clonotypes identified per sample. In total, 29/34, 40/40, 22/22 and 9/9 known functional TRAV, TRAJ, TRBV and TRBJ gene segments are observed respectively. Pseudogene or otherwise defective gene segments are also detected supporting re-annotation of several as functional. Healthy dogs exhibit highly diverse repertoires, T cell lymphomas exhibit clonal repertoires, and vaccine-treated melanoma dogs are dominated by a small number of highly abundant clonotypes. scRNA libraries define large clusters of V(D)J-expressing CD8+ and CD4 + T cells. Dominant clonotypes observed in melanoma PBMCs are predominantly CD8 + T cells, with activated phenotypes, suggesting possible anti-tumor T cell populations.
Topics: Animals; Dogs; Receptors, Antigen, T-Cell; Single-Cell Analysis; Melanoma; Dog Diseases; Lymphoma, T-Cell
PubMed: 38649520
DOI: 10.1038/s42003-024-06174-w -
Genomics May 2024Mitochondria play an important role in the energy production of plant cells through independent genetic systems. This study has aimed to assemble and annotate the... (Review)
Review
Mitochondria play an important role in the energy production of plant cells through independent genetic systems. This study has aimed to assemble and annotate the functions of the mitochondrial (mt) genome of Luffa cylindrica. The mt genome of L. cylindrica contained two chromosomes with lengths of 380,879 bp and 67,982 bp, respectively. Seventy-seven genes including 39 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 pseudogene, were identified. About 90.63% of the codons ended with A or U bases, and 98.63% of monomers contained A/T, which contributed to the high A/T content (55.91%) of the complete mt genome. Six genes (ATP8, CCMFC, NAD4, RPL10, RPL5 and RPS4) showed positive selection. Phylogenetic analysis indicates that L. cylindrica is closely related to L. acutangula. The present results provide the mt genome of L. cylindrica, which may facilitate possible genetic variation, evolutionary, and molecular breeding studies of L. cylindrica.
Topics: Genome, Mitochondrial; Phylogeny; Luffa; RNA, Transfer; Genome, Plant; Plant Proteins
PubMed: 38750703
DOI: 10.1016/j.ygeno.2024.110859 -
Molecular Therapy : the Journal of the... Jun 2024Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among...
Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.
Topics: Keloid; Humans; RNA, Long Noncoding; Extracellular Matrix; CCAAT-Enhancer-Binding Proteins; Animals; Mice; Gene Expression Regulation; Fibroblasts; Promoter Regions, Genetic; Male; Up-Regulation
PubMed: 38553852
DOI: 10.1016/j.ymthe.2024.03.031 -
Cells Aug 2023Fatal familial insomnia (FFI) is a rare autosomal-dominant inherited prion disease with a wide variability in age of onset. Its causes are not known. In the present...
Fatal familial insomnia (FFI) is a rare autosomal-dominant inherited prion disease with a wide variability in age of onset. Its causes are not known. In the present study, we aimed to analyze genetic risk factors other than the prion protein gene (), in FFI patients with varying ages of onset. Whole-exome sequencing (WES) analysis was performed for twenty-five individuals with FFI (D178N-129M). Gene ontology enrichment analysis was carried out by Reactome to generate hypotheses regarding the biological processes of the identified genes. In the present study, we used a statistical approach tailored to the specifics of the data and identified nineteen potential gene variants with a potential effect on the age of onset. Evidence for potential disease modulatory risk loci was observed in two pseudogenes ( and three protein coding genes and . These genetic variants are absent in FFI patients with early disease onset (19-40 years). The biological function of these genes and is associated with programmed cell death, caspase-mediated cleavage of cytoskeletal proteins and apoptotic cleavage of cellular proteins. In conclusions, our study provided first evidence for the involvement of genetic risk factors additional to , which may influence the onset of clinical symptoms in FFI.
Topics: Humans; Insomnia, Fatal Familial; Exome Sequencing; Age of Onset; Genes, Regulator; Prions; Prion Proteins
PubMed: 37626863
DOI: 10.3390/cells12162053 -
G3 (Bethesda, Md.) Jul 2023The Rock Ptarmigan (Lagopus muta) is a cold-adapted, largely sedentary, game bird with a Holarctic distribution. The species represents an important example of an...
The Rock Ptarmigan (Lagopus muta) is a cold-adapted, largely sedentary, game bird with a Holarctic distribution. The species represents an important example of an organism likely to be affected by ongoing climatic shifts across a disparate range. We provide here a high-quality reference genome and mitogenome for the Rock Ptarmigan assembled from PacBio HiFi and Hi-C sequencing of a female bird from Iceland. The total size of the genome is 1.03 Gb with a scaffold N50 of 71.23 Mb and a contig N50 of 17.91 Mb. The final scaffolds represent all 40 predicted chromosomes, and the mitochondria with a BUSCO score of 98.6%. Gene annotation resulted in 16,078 protein-coding genes out of a total 19,831 predicted (81.08% excluding pseudogenes). The genome included 21.07% repeat sequences, and the average length of genes, exons, and introns were 33605, 394, and 4265 bp, respectively. The availability of a new reference-quality genome will contribute to understanding the Rock Ptarmigan's unique evolutionary history, vulnerability to climate change, and demographic trajectories around the globe while serving as a benchmark for species in the family Phasianidae (order Galliformes).
Topics: Animals; Female; Quail; Galliformes; Repetitive Sequences, Nucleic Acid; Chromosomes; Genome; Phylogeny
PubMed: 37141262
DOI: 10.1093/g3journal/jkad099 -
Genes Aug 2023The reproductive homeobox on the X chromosome (RHOX) genes were first identified in the mouse during the 1990s and have a crucial role in reproduction. In various... (Review)
Review
The reproductive homeobox on the X chromosome (RHOX) genes were first identified in the mouse during the 1990s and have a crucial role in reproduction. In various transcription factors with a key regulatory role, the homeobox sequence encodes a "homeodomain" DNA-binding motif. In the mouse, there are three clusters of Rhox genes (α, β, and γ) on the X chromosome. Each cluster shows temporal and/or quantitative collinearity, which regulates the progression of the embryonic development process. Although the RHOX family is conserved in mammals, the interspecies differences in the number of RHOX genes and pseudogenes testifies to a rich evolutionary history with several relatively recent events. In the mouse, Rhox genes are mainly expressed in reproductive tissues, and several have a role in the differentiation of primordial germ cells (, , and ) and in spermatogenesis (, , and ). Despite the lack of detailed data on human RHOX, these genes appear to be involved in the formation of germ cells because they are predominantly expressed during the early () and late () stages of germ cell development. Furthermore, the few variants identified to date are thought to induce or predispose to impaired spermatogenesis and severe oligozoospermia or azoospermia. In the future, research on the pathophysiology of the human RHOX genes is likely to confirm the essential role of this family in the reproductive process and might help us to better understand the various causes of infertility and characterize the associated human phenotypes.
Topics: Male; Pregnancy; Female; Humans; Animals; Mice; Genes, Homeobox; Homeodomain Proteins; Multigene Family; Transcription Factors; Spermatogenesis; Mammals
PubMed: 37761825
DOI: 10.3390/genes14091685 -
Mitochondrial DNA. Part B, Resources 2023Miq. is a deciduous arbor and a member of Sabiaceae. It is one of the rare and protected plants with outstanding ornamental and economic value in Jiangsu, China. In...
Miq. is a deciduous arbor and a member of Sabiaceae. It is one of the rare and protected plants with outstanding ornamental and economic value in Jiangsu, China. In addition to the resource values indicated above, there are numerous other elements that require additional research, including the chloroplast (cp) genomic information. In this work, the complete cp genome sequence of was assembled and characterized for the first time. The complete cp genome of was 159,950 base pair (bp) in length, including a large single-copy (LSC) region of 87,147 bp, a small single-copy (SSC) region of 18,015 bp, and the inverted repeats (IRs) region of 27,394 bp. It contains 131 genes, including 37 tRNA genes, eight rRNA genes, 85 protein-coding genes, and one pseudogene. The overall GC content of cp genome was 37.95%. The placement of in the phylogenetic tree constructed using the complete cp genome is largely congruent with previous studies. The clustering of is non-monophyletic, aligns more closely with existing morphological taxonomic studies, thereby enhancing the scholarly and scientific nature of this research.
PubMed: 38188441
DOI: 10.1080/23802359.2023.2281034 -
BMC Genomics Dec 2023Chiloschista (Orchidaceae, Aeridinae) is an epiphytic leafless orchid that is mainly distributed in tropical or subtropical forest canopies. This rare and threatened...
BACKGROUND
Chiloschista (Orchidaceae, Aeridinae) is an epiphytic leafless orchid that is mainly distributed in tropical or subtropical forest canopies. This rare and threatened orchid lacks molecular resources for phylogenetic and barcoding analysis. Therefore, we sequenced and assembled seven complete plastomes of Chiloschista to analyse the plastome characteristics and phylogenetic relationships and conduct a barcoding investigation.
RESULTS
We are the first to publish seven Chiloschista plastomes, which possessed the typical quadripartite structure and ranged from 143,233 bp to 145,463 bp in size. The plastomes all contained 120 genes, consisting of 74 protein-coding genes, 38 tRNA genes and eight rRNA genes. The ndh genes were pseudogenes or lost in the genus, and the genes petG and psbF were under positive selection. The seven Chiloschista plastomes displayed stable plastome structures with no large inversions or rearrangements. A total of 14 small inversions (SIs) were identified in the seven Chiloschista plastomes but were all similar within the genus. Six noncoding mutational hotspots (trnN-rpl32 > rpoB-trnC > psbK-psbI > psaC-rps15 > trnE-trnT > accD-psaI) and five coding sequences (ycf1 > rps15 > matK > psbK > ccsA) were selected as potential barcodes based on nucleotide diversity and species discrimination analysis, which suggested that the potential barcode ycf1 was most suitable for species discrimination. A total of 47-56 SSRs and 11-14 long repeats (> 20 bp) were identified in Chiloschista plastomes, and they were mostly located in the large single copy intergenic region. Phylogenetic analysis indicated that Chiloschista was monophyletic. It was clustered with Phalaenopsis and formed the basic clade of the subtribe Aeridinae with a moderate support value. The results also showed that seven Chiloschista species were divided into three major clades with full support.
CONCLUSION
This study was the first to analyse the plastome characteristics of the genus Chiloschista in Orchidaceae, and the results showed that Chiloschista plastomes have conserved plastome structures. Based on the plastome hotspots of nucleotide diversity, several genes and noncoding regions are suitable for phylogenetic and population studies. Chiloschista may provide an ideal system to investigate the dynamics of plastome evolution and DNA barcoding investigation for orchid studies.
Topics: Phylogeny; DNA Barcoding, Taxonomic; Orchidaceae; Genome, Plastid; Nucleotides; Genome, Chloroplast
PubMed: 38057701
DOI: 10.1186/s12864-023-09847-8 -
Genome Biology and Evolution Nov 2023Olfactory receptor (OR) genes represent the largest multigenic family in mammalian genomes and encode proteins that bind environmental odorant molecules. The OR...
Olfactory receptor (OR) genes represent the largest multigenic family in mammalian genomes and encode proteins that bind environmental odorant molecules. The OR repertoire is extremely variable among species and is subject to many gene duplications and losses, which have been linked to ecological adaptations in mammals. Although they have been studied on a broad taxonomic scale (i.e., placental), finer sampling has rarely been explored in order to better capture the mechanisms that drove the evolution of the OR repertoire. Among placental mammals, rodents are well-suited for this task, as they exhibit diverse life history traits, and genomic data are available for most major families and a diverse array of lifestyles. In this study, 53 rodent published genomes were mined for their OR subgenomes. We retrieved more than 85,000 functional and pseudogene OR sequences that were subsequently classified into phylogenetic clusters. Copy number variation among rodents is similar to that of other mammals. Using our OR counts along with comparative phylogenetic approaches, we demonstrated that ecological niches such as diet, period of activity, and a fossorial lifestyle strongly impacted the proportion of OR pseudogenes. Within the OR subgenome, phylogenetic inertia was the main factor explaining the relative variations of the 13 OR gene families. However, a striking exception was a convergent 10-fold expansion of the OR family 14 among the phylogenetically divergent subterranean mole-rat lineages belonging to Bathyergidae and Spalacidae families. This study illustrates how the diversity of the OR repertoire has evolved among rodents, both shaped by selective forces stemming from species life history traits and neutral evolution along the rodent phylogeny.
Topics: Female; Pregnancy; Animals; Phylogeny; Rodentia; DNA Copy Number Variations; Receptors, Odorant; Placenta; Mammals; Evolution, Molecular
PubMed: 37972291
DOI: 10.1093/gbe/evad197