Long-read sequencing technologies such as isoform sequencing can generate highly accurate sequences of full-length mRNA transcript isoforms. Such long-read transcriptomics may be especially useful in investigations of lymphocyte functional plasticity as it relates to human health and disease. However, no long-read isoform-aware reference transcriptomes of human circulating lymphocytes are readily available despite being valuable as benchmarks in a variety of transcriptomic studies. To begin to fill this gap, we purified 4 lymphocyte populations (CD4+ T, CD8+ T, NK, and Pan B cells) from the peripheral blood of a healthy male donor and obtained high-quality RNA (RIN > 8) for isoform sequencing and parallel RNA-Seq analyses. Many novel polyadenylated transcript isoforms, supported by both isoform sequencing and RNA-Seq data, were identified within each sample. The datasets met several metrics of high quality and have been deposited to the Gene Expression Omnibus database (GSE202327, GSE202328, GSE202329) as both raw and processed files to serve as long-read reference transcriptomes for future studies of human circulating lymphocytes.
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http://dx.doi.org/10.1093/g3journal/jkac253 | DOI Listing |
Sci Rep
December 2024
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occur. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression.
View Article and Find Full Text PDFJ Med Chem
December 2024
Institute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Members of the casein kinase 1 (CK1) family have emerged as key regulators of cellular signaling and as potential drug targets. Functional annotation of the 7 human isoforms would benefit from isoform-selective inhibitors, allowing studies on the role of these enzymes in normal physiology and disease pathogenesis. However, due to significant sequence homology within the catalytic domain, isoform selectivity is difficult to achieve with conventional small molecules.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada. Electronic address:
Calpain-3 is an intracellular Ca-dependent cysteine protease abundant in skeletal muscle. Loss-of-function mutations in its single-copy gene cause a dystrophy of the limb-girdle muscles. These mutations, of which there are over 500 in humans, are spread all along this 94-kDa multi-domain protein that includes three 40+-residue sequences (NS, IS1, and IS2).
View Article and Find Full Text PDFFree Radic Biol Med
December 2024
Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University), 400038, Chongqing, China; State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), 400038, Chongqing, China. Electronic address:
Spaceflight-induced osteoporosis (SFOP) is a detrimental healthcare consequence during spaceflight. Weightlessness and ionizing radiation were main environmental factors that contribute to SFOP, especially in the manned deep space voyages. However, currently there is scarce effective method to treat SFOP.
View Article and Find Full Text PDFMol Ther Oncol
December 2024
Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, USA.
Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor () to the proliferative isoform.
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