当前共找到 2 篇文献分享。
1.
翁凯
(2025-03-05 21:45):
#paper 【doi】10.1038/s41586-024-07954-4；【发表年份】2024年；【期刊】Nature；【标题】Temporal recording of mammalian development and precancer。该研究旨在突破传统细胞事件追踪技术的局限性，通过开发基于CRISPR的单细胞分子钟平台，实现哺乳动物发育和肿瘤起源的精准时空记录。研究者利用自突变CRISPR条形码技术，在单细胞水平同步捕获基因表达和遗传变异信息，系统解析了小鼠胚胎器官形成过程中细胞增殖、分化和克隆动态，揭示出肠道发育中未被识别的新型祖细胞群体及其功能特征。进一步将此技术应用于人类结直肠癌前病变样本（包含116个息肉的转录组和418个息肉的突变组数据），首次证实约15-30%的腺瘤起源于多个独立正常干细胞，挑战了传统单克隆致癌假说，为癌症早期起源机制研究提供了多维证据支持。
2.
翁凯
(2025-03-02 17:41):
#paper doi：10.1038/s41587-024-02248-6；发表年份：2024；期刊：Nature Biotechnology；标题：High-throughput discovery of MHC class I- and II-restricted T cell epitopes using synthetic cellular circuits。传统抗原检测技术依赖人类原代T细胞，只能识别少数MHC类型（如人类MHC I类），且无法高效分析低亲和力抗原或跨物种（如小鼠）模型。为了解决这些问题，本研究开发了名为TCR-MAP的新技术，其核心是通过基因工程改造Jurkat细胞（一种实验室常用的T细胞系），使其携带特定T细胞受体（TCR）和一个名为Sortase A的酶；当TCR识别到抗原呈递细胞（如病毒感染的细胞或肿瘤细胞）表面的抗原肽-MHC复合物时，Sortase A会被激活，并在靶细胞表面打上生物素“标记”，随后通过磁珠富集这些标记细胞并测序解析抗原。实验证明，该技术能同时兼容人类和小鼠的MHC I/II类抗原，成功识别了CMV病毒抗原、肿瘤抗原（如CTAG1B）以及自身免疫疾病相关抗原（如心脏中的CKMT2），检测灵敏度达到微摩尔级（可发现极微量的抗原），且无需依赖不稳定的原代T细胞。这一平台为病毒逃逸研究、肿瘤疫苗开发和自身免疫病机制解析提供了高效工具，未来还可扩展至脂类等非蛋白抗原的检测。
Nature Biotechnology,
2024-7-2.
DOI: 10.1038/s41587-024-02248-6
Abstract:
AbstractAntigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. …
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AbstractAntigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity.
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