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This study reports the use of single-cell RNA sequencing to evaluate B cells in the peripheral blood mononuclear cells (PBMCs) and intrathyroidal blood mononuclear cells of patients with Graves' disease (GD) undergoing thyroidectomy. These cells were stimulated with overlapping peptides of thyroid autoantigens, including thyroid-stimulating hormone receptor (TSHR), thyroglobulin (Tg), and thyroid peroxidase (TPO). In PBMCs, naive B cells are characterized by and , whereas memory B cells express , , and . , , , , , , and expression increased in peptide-stimulated naive and memory B cells compared to those in the controls. Thyroid naive B cells are characterized by and , whereas memory B cells express , , and Thyroid B cells showed higher , , , , , and immunoglobulin gene expression than control PBMCs and thyroid cells. B-cell receptor analysis revealed frequent and usage in controls, whereas expression was increased in TSHR-stimulated groups. We concluded that B-cell responses to TSHR, Tg, and TPO differed and that changes in B-cell reactivity also occurred in PBMCs and the thyroid. Additionally, and may be associated with autoantibody production in GD.
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http://dx.doi.org/10.3390/cells14141102 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
J Clin Invest
September 2025
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom.
Understanding the genetic causes of diseases affecting pancreatic β cells and neurons can give insights into pathways essential for both cell types. Microcephaly, epilepsy and diabetes syndrome (MEDS) is a congenital disorder with two known aetiological genes, IER3IP1 and YIPF5. Both genes encode proteins involved in endoplasmic reticulum (ER) to Golgi trafficking.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
View Article and Find Full Text PDFRNA Biol
September 2025
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
Neural stem cells (NSCs) are multipotent stem cells with self-renewal capacity, able to differentiate into all neural lineages of the central nervous system, including neurons, oligodendrocytes, and astrocytes; thus, their proliferation and differentiation are essential for embryonic neurodevelopment and adult brain homoeostasis. Dysregulation in these processes is implicated in neurological disorders, highlighting the need to elucidate how NSCs proliferate and differentiate to clarify the mechanisms of neurogenesis and uncover potential therapeutic targets. MicroRNAs (miRNAs) are small, post-transcriptional regulators of gene expression involved in many aspects of nervous system development and function.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
School of Medicine, Chongqing University, Chongqing 400044, China.
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion.
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