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SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 () in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.
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http://dx.doi.org/10.1073/pnas.2117112119 | DOI Listing |
Cell Rep
September 2025
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
Progranulin-deficient frontotemporal dementia (GRN-FTD) is a major cause of familial FTD with TAR DNA-binding protein 43 (TDP-43) pathology, which is linked to exon dysregulation. However, little is known about this dysregulation in glial and neuronal cells. Here, using splice-junction-covering enrichment probes, we introduce single-nuclei long-read RNA sequencing 2 (SnISOr-Seq2), targeting 3,630 high-interest genes without loss of precision, and complete the first single-cell, long-read-resolved case-control study for neurodegeneration.
View Article and Find Full Text PDFJ Biol Chem
September 2025
School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chines
Long non-coding RNAs (lncRNAs) play crucial roles in plant growth, development, and stress responses. With the advancement of single-cell RNA sequencing (scRNA-seq) technology, it is now possible to investigate lncRNA expression and function at single-cell resolution. Although several plant single-cell transcriptome databases have been established, they predominantly focus on protein-coding genes while largely overlooking lncRNAs.
View Article and Find Full Text PDFAgeing Res Rev
September 2025
Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, USA; Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.
Body-brain interaction (BBI) plays a critical role in coordinating the communication between peripheral organs and the brain, contributing to the comorbidity of metabolic disorders and neurological disorders. In the context of obesity, one of the key mediators driving systemic and neuroinflammatory responses is the soluble form of tumor necrosis factor (TNF), which primarily signals through TNF receptor 1 (TNFR1) to regulate inflammation and cell death. In this review, we examine how TNF/TNFR1-mediated metabolic inflammation in obesity disrupts cellular homeostasis across multiple organ systems, including the brain.
View Article and Find Full Text PDFCell Rep
September 2025
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to meet the evolving demands of an organism. Adult human MPPs remain ill defined, whereas mouse MPPs are well characterized, with distinct immunophenotypes and lineage potencies. Using multi-omic single-cell analyses and functional assays, we identified distinct human MPPs within Lin-CD34+CD38dim/lo adult bone marrow with unique biomolecular and functional properties.
View Article and Find Full Text PDFSTAR Protoc
September 2025
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensiv
DNA replication timing (RT) is the cell-type-specific order by which different genomic regions are replicated during the S phase. Here, we present a biotinylation-based version of Repli-seq (BioRepli-seq) to determine genome-wide RT through next-generation sequencing. We detail steps for nucleotide analog pulse labeling, DNA content-based cell sorting, click chemistry-based biotinylation, DNA fragmentation, and on-bead sequencing library generation.
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