XinLab

多组学整合解析野生放线菌结瘤植物根瘤菌群的复杂性与弗兰克氏菌共生特性

Fri, 10 Apr 2026 20:00:00 +0800

放线菌结瘤植物是温带生态系统中的重要先锋物种，它们与弗兰克氏菌（Frankiaceae）形成固氮根瘤共生，贡献了全球约 25% 的陆地生物固氮量。然而，与研究透彻的豆科植物–根瘤菌共生相比，它们的根系微生物组在很大程度上仍是空白。在我们最近发表于《New Phytologist》的研究中，我们整合 16S 扩增子、转录组和宏基因组数据，对野生放线菌结瘤植物、豆科植物及非结瘤近缘种的根瘤微生物组进行了系统解析，揭示了这类共生关系的组装方式及其与豆科植物的根本差异。

我们做了什么

我们利用 16S rDNA 测序，对五个系统发育上具有代表性的放线菌结瘤物种（覆盖全部三个放线菌结瘤目）以及三种豆科植物和四种非结瘤固氮分支（NFC）物种的根际、根和根瘤三个区室的原核群落进行了分析。随后对放线菌结瘤植物的根进行了转录组分析，对根瘤进行了宏基因组分析，并从宏基因组组装基因组（MAG）中恢复了四个新的弗兰克氏菌物种。

关键发现

弗兰克氏菌很少在根瘤中占据绝对优势。 与豆科根瘤中根瘤菌通常 >95% 的相对丰度不同，放线菌结瘤植物根瘤中弗兰克氏菌的丰度波动较大，很少超过 90%——这是”更松散”、更不亲密共生的直接证据。
根瘤内存在多样且以正相互作用为主的微生物联合体。 放线菌结瘤根瘤中含有大量非弗兰克氏菌类群（43 个科），85.8% 的微生物相关性为正。弗兰克氏菌形成紧密互作的亚群（模块 2），同时还有链霉菌科和 Solirubrobacterales 等功能成员——后者是首次在放线菌结瘤根瘤中报道。
放线菌结瘤植物主动招募特化的根际群落。 它们富集有益微生物，尤其是氨氧化古菌（Nitrososphaeraceae），这可能加速贫瘠土壤中的氮循环——与该类植物的先锋生活史策略相吻合。
保守的共生工具箱，但有其独特之处。 在 203 个经过验证的豆科根瘤共生（RNS）基因中，110 个在放线菌结瘤各目中普遍表达，包括完整的共生信号通路。值得注意的是，一个近乎完整的磷酸肌醇（PI）信号模块与弗兰克氏菌丰度显著相关，提示 PI 信号可能参与放线菌共生的信号转导。
弗兰克氏菌与根瘤菌在共生功能上存在根本差异。 其较不亲密的共生关系可能有利于温带多年生放线菌结瘤植物的生活史策略，对理解固氮共生的演化具有重要意义。

意义

这项工作提供了放线菌结瘤根瘤微生物组的首个多组学全景，凸显了固氮共生中既保守又分化的特征，并为研究和潜在改造固氮共生提供了新资源——包括新的弗兰克氏菌基因组。

论文： Luo X, Lei Z, Fang D, Chen H, Qian L, Jin C, Wang X, Liu X, Liu H, Wang Y. Integrated multi-omics decipher the complex nodule microbiota and distinct Frankiaceae symbiotic traits in wild actinorhizal plants. New Phytologist 2026;251:2832–2851. DOI: 10.1111/nph.71234

Integrated Multi-Omics Decipher the Complex Nodule Microbiota and Distinct Frankiaceae Symbiotic Traits in Wild Actinorhizal Plants

Fri, 10 Apr 2026 20:00:00 +0800

Actinorhizal plants—woody pioneers of temperate ecosystems—form nitrogen-fixing root nodules with Frankiaceae bacteria, contributing roughly 25% of terrestrial biological nitrogen input. Yet compared with the well-studied legume–rhizobia symbiosis, their root-associated microbiomes have remained largely uncharted. In our latest study published in New Phytologist, we integrated 16S amplicon, transcriptomic, and metagenomic data across wild actinorhizal plants, legumes, and non-nodulating relatives to reveal how these symbioses are assembled—and how they differ fundamentally from legumes.

What We Did

We profiled the prokaryotic communities in the rhizosphere, root, and nodule compartments of five phylogenetically representative actinorhizal species (spanning all three actinorhizal orders), three legumes, and four non-nodulating nitrogen-fixing-clade (NFC) species using 16S rDNA sequencing. We then performed transcriptomic analysis on actinorhizal roots and metagenomic analysis on nodules, recovering four novel Frankiaceae species from metagenome-assembled genomes (MAGs).

Key Findings

Frankiae rarely dominate nodules. Unlike rhizobia in legume nodules (typically >95% relative abundance), Frankiaceae abundance in actinorhizal nodules fluctuated and rarely exceeded 90%—evidence of a “looser,” less intimate symbiosis.
Nodules harbour a diverse, positively interacting microbial consortium. Actinorhizal nodules contain many non-Frankiaceae bacteria (43 families), with 85.8% of microbial correlations being positive. Frankiae formed a tightly interconnected subgroup (Module 2), alongside other functional players such as Streptomycetaceae and Solirubrobacterales—the latter reported in actinorhizal nodules for the first time.
Actinorhizal plants actively recruit a specialized rhizosphere community. They enrich beneficial microbes, notably ammonia-oxidising archaea (Nitrososphaeraceae), which may accelerate nitrogen cycling in nutrient-poor soils—matching the pioneer lifestyle of these plants.
A conserved symbiotic toolkit, with a twist. 110 of 203 validated legume RNS genes were ubiquitously expressed across actinorhizal orders, including the entire common symbiosis signalling pathway. Notably, a nearly complete phosphoinositide (PI) signalling module correlated with Frankiaceae abundance, suggesting PI signalling functions in actinorhizal symbiotic signal transduction.
Frankiaceae differ fundamentally from rhizobia in symbiotic function. Their less intimate symbiosis may favour the life-history strategies of temperate perennial actinorhizal plants, with implications for understanding the evolution of nitrogen-fixing symbioses.

Why It Matters

This work provides the first comprehensive multi-omics view of actinorhizal nodule microbiomes, highlights both conserved and divergent features of nitrogen-fixing symbioses, and offers new resources—including novel Frankiaceae genomes—for studying and potentially engineering nitrogen-fixing associations.

Paper: Luo X, Lei Z, Fang D, Chen H, Qian L, Jin C, Wang X, Liu X, Liu H, Wang Y. Integrated multi-omics decipher the complex nodule microbiota and distinct Frankiaceae symbiotic traits in wild actinorhizal plants. New Phytologist 2026;251:2832–2851. DOI: 10.1111/nph.71234

单核转录组图谱揭示癫痫发生过程中的细胞与分子变化

Sun, 01 Mar 2026 20:00:00 +0800

癫痫影响着全球约1%的人口，约30%的患者无法通过现有抗癫痫药物实现完全控制。一大障碍是我们对”癫痫发生”（epileptogenesis）——正常大脑转变为癫痫大脑的过程——仍缺乏完整的理解。在我们最近发表于《Neuroscience Bulletin》的合作研究中，我们构建了迄今最全面的癫痫发生单核转录组图谱，覆盖了疾病三个阶段的三个脑区。

我们做了什么

利用单核RNA测序（snRNA-seq），我们对毛果芸香碱诱导的颞叶癫痫（TLE）大鼠模型的海马、颞叶皮层和丘脑，在急性期（24小时）、潜伏期（7天）和慢性期（8周）及对照组中进行了全面分析。共获得 311,177 个单核（来自36个样本），注释出九大类细胞。

关键发现

急性期海马变化最剧烈。 急性期各脑区的差异表达基因（DEG）数量最多（1,775个），其中海马最多（1,007个），提示癫痫发生启动时海马发生强烈的分子变化。
潜伏期是丘脑”隐藏的重塑窗口”。 在尚无临床发作的潜伏期，丘脑的DEG数量最多（789个，其中707个上调），富集于突触组织与膜电位调控相关通路。这表明潜伏期是干预的关键时间窗口，且丘脑的作用远超以往的认知。
急性期出现两个新型星形胶质细胞簇。 亚聚类分析发现两个星形胶质细胞亚群（Cluster 3 和 Cluster 9）在急性期特异扩增，存在于全部三个脑区，其中海马丰度最高。
EX–Astro C3–IN 通路或成为潜在干预靶点。 细胞通讯分析揭示了海马急性期特异的级联通路：兴奋性神经元通过 SPP1 信号作用于星形胶质细胞 Cluster 3，后者再通过 EGF 信号作用于抑制性神经元。该通路可能参与了神经元过度兴奋，是未来治疗干预的潜在靶点。

意义

这一数据集以单细胞分辨率提供了癫痫发生的时空全景，凸显了潜伏期与丘脑作为早期干预靶点的重要性，也为”在癫痫发作前阻止其发生”提供了新的分子切入点。

论文： Wang Y, Wang Y, Yu F, Liu Y, Liu X, Cai Z. Single-Nucleus Transcriptomic Sequencing Revealed Cellular and Molecular Changes in a Pilocarpine-Induced Epilepsy Rat Model. Neuroscience Bulletin 2026;42(3):539–558. DOI: 10.1007/s12264-025-01451-y

Single-Nucleus Transcriptomic Atlas Reveals Cellular and Molecular Changes During Epileptogenesis

Sun, 01 Mar 2026 20:00:00 +0800

Epilepsy affects about 1% of the global population, and roughly 30% of patients do not achieve complete seizure control with existing antiseizure medications. A major obstacle is that we still do not fully understand epileptogenesis—the process by which a normal brain transforms into an epileptic one. In our latest collaborative study published in Neuroscience Bulletin, we built the most comprehensive single-nucleus transcriptomic atlas of epileptogenesis to date, covering three brain regions across all three phases of the disease.

What We Did

Using single-nucleus RNA sequencing (snRNA-seq), we profiled the hippocampus, temporal cortex, and thalamus in a pilocarpine-induced rat model of temporal lobe epilepsy (TLE) across the acute (24 h), latent (7 d), and chronic (8 w) phases, together with controls. In total, we obtained 311,177 single nuclei from 36 samples and annotated nine major cell types.

Key Findings

The acute phase hits the hippocampus hardest. The acute phase showed the highest number of differentially expressed genes (DEGs) across all regions (1,775), with the hippocampus leading (1,007 DEGs)—pointing to intense molecular changes at the onset of epileptogenesis.
The latent phase is a hidden window of remodeling in the thalamus. During the latent phase—when no seizures are yet visible—the thalamus displayed the most DEGs (789, with 707 upregulated), enriched in synapse organization and membrane potential regulation. This suggests the latent phase is a critical, and potentially actionable, window for intervention, with the thalamus playing a much greater role than previously appreciated.
Two novel astrocyte clusters emerge in the acute phase. Subclustering revealed two astrocyte populations (Cluster 3 and Cluster 9) that expanded specifically in the acute phase across all three brain regions, with the highest abundance in the hippocampus.
A specific EX–Astro C3–IN pathway as a potential intervention target. Cell-cell communication analysis uncovered a hippocampus-specific acute-phase cascade: excitatory neurons signal to astrocyte Cluster 3 via SPP1, which in turn signals to inhibitory neurons via EGF. This pathway may contribute to hyperexcitability and represents a promising target for future therapies.

Why It Matters

This dataset provides a detailed temporal and spatial view of epileptogenesis at single-cell resolution, highlighting the latent phase and the thalamus as key targets for early intervention—and offering new molecular entry points to stop epilepsy before it starts.

Paper: Wang Y, Wang Y, Yu F, Liu Y, Liu X, Cai Z. Single-Nucleus Transcriptomic Sequencing Revealed Cellular and Molecular Changes in a Pilocarpine-Induced Epilepsy Rat Model. Neuroscience Bulletin 2026;42(3):539–558. DOI: 10.1007/s12264-025-01451-y

单核与空间转录组揭示毛竹居间分生组织的细胞类群

Thu, 18 Dec 2025 20:00:00 +0800

世界上生长最快的植物一天能蹿升一米多，其秘密藏在竹秆内部的”居间分生组织”（IcM）——一个持续分裂、伸长长达 45–60 天的特化生长区。然而这些细胞一直极难研究：它们活动期短暂、深埋于成熟组织中，且在典型的模式物种中并不存在。在我们最近发表于《PNAS》的研究中，我们构建了毛竹居间分生组织的首个单细胞图谱，揭示了其中隐藏的细胞类群及其爆发式生长背后的干细胞机制。

我们做了什么

以一天最快生长 114.5 厘米 的毛竹（Phyllostachys edulis）为材料，我们将染色体水平基因组组装与单核 RNA 测序（snRNA-seq）、Stereo-seq 空间转录组、ATAC-seq 和高分辨率解剖成像相结合，覆盖三个发育阶段：初始分裂期（ID）、快速分裂期（RD）和快速伸长期（RE）。

128,370 个高质量单核，鉴定出 13 个单核细胞亚群（snClusters），覆盖 96.6% 的注释基因
Stereo-seq 解析出七个空间区域，与解剖注释高度一致（Jaccard 指数 = 88.7%）

关键发现

IcM 细胞是嵌在基本组织薄壁细胞（Gp）之间的短柱状细胞。 结合空间转录组、原位杂交和扫描电镜，我们揭示了其独特的形态特征：薄细胞壁、明显的角隅结构，以及特征性的细胞壁内陷。
IcM1 是一个干细胞样亚群。 在三个 IcM 亚型（IcM1–3）中，IcM1 具有最高的干性评分（CytoTRACE），表达包括多个 WOX 家族成员在内的干细胞身份基因，并在转录水平上类似于茎尖分生组织的原形成层富集域（PED）。值得注意的是，占细胞总数仅约 15% 的 IcM1 贡献了全部 WOX2 转录本高达 67% 的表达。
一个 WOX2 同源基因驱动再生。 在竹源愈伤组织中过表达 clrGene008562（WOX2 同源基因）可显著促进增殖与分化——提示它是 IcM 中调控细胞分裂与命运决定的保守因子。
双分支的发育轨迹。 拟时分析显示，IcM1 细胞要么经由过渡态分化为 Gp 细胞，要么成熟为稳定的未分化状态；两条分支分别由不同的共表达模块调控（细胞周期调控因子如 CDKB2-1、CYCB1-5 对胁迫/适应调控因子如 ERF、LBD）。

意义

这项工作为理解居间分生组织如何驱动竹子非凡的生长——以及更广泛地，单子叶植物如何调控快速茎秆伸长——提供了分子与细胞层面的框架。文中多组学资源（含在线交互图谱：https://db.cngb.org/stomics/datasets/STDS0000377）为提升作物生产力和发展可持续生物材料奠定了基础。

论文： Qin N, Liu X, Li S, Sun L, Chen C, et al. Single-nucleus and spatial transcriptomics reveal the cell populations of intercalary meristems in bamboo. PNAS 2025;122(51):e2511701122. DOI: 10.1073/pnas.2511701122

Single-Nucleus and Spatial Transcriptomics Reveal the Cell Populations of Intercalary Meristems in Bamboo

Thu, 18 Dec 2025 20:00:00 +0800

How does the world’s fastest-growing plant shoot up by more than a meter in a single day? The answer lies in the intercalary meristem (IcM)—a specialized growth zone inside the bamboo culm that keeps dividing and elongating for 45–60 days. Yet these cells have been notoriously hard to study: they are transient, deeply embedded in mature tissue, and absent from typical model species. In our latest study published in PNAS, we built the first comprehensive single-cell atlas of the bamboo IcM, revealing its hidden cell populations and the stem-cell machinery behind its explosive growth.

What We Did

Using Moso bamboo (Phyllostachys edulis)—which grows up to 114.5 cm per day—we integrated a chromosome-level genome assembly with single-nucleus RNA sequencing (snRNA-seq), Stereo-seq spatial transcriptomics, ATAC-seq, and high-resolution anatomical imaging across three developmental stages: initial division (ID), rapid division (RD), and rapid elongation (RE).

128,370 high-confidence nuclei, 13 distinct single-nucleus clusters (snClusters), covering 96.6% of annotated genes
Seven spatially defined zones resolved by Stereo-seq, with high concordance with anatomical annotations (Jaccard index = 88.7%)

Key Findings

IcM cells are short-columnar cells nestled among ground tissue parenchyma (Gp) cells. Combined spatial transcriptomics, in situ hybridization, and scanning electron microscopy revealed their distinctive morphology: thin cell walls, corner domains, and characteristic wall invaginations.
IcM1 is a stem-like subpopulation. Among the three IcM subtypes (IcM1–3), IcM1 showed the highest stemness score (CytoTRACE), expressed stem-cell identity genes including multiple WOX family members, and transcriptionally resembled the procambium-enriched domain (PED) of the shoot apical meristem. Notably, up to 67% of all WOX2 transcripts came from IcM1 cells, which make up only ~15% of the cell population.
A WOX2 homolog drives regeneration. Overexpressing clrGene008562 (a WOX2 homolog) in bamboo-derived callus significantly promoted both proliferation and differentiation—pointing to a conserved regulator of cell division and fate determination in the IcM.
A bifurcated developmental trajectory. Pseudotime analysis showed IcM1 cells either differentiate into Gp cells (via a transitional state) or mature into a stabilized, undifferentiated state, with distinct co-expression modules (cell-cycle regulators like CDKB2-1 and CYCB1-5 vs. stress/adaptation regulators like ERF and LBD) governing each branch.

Why It Matters

This work provides a molecular and cellular framework for understanding how intercalary meristems drive the extraordinary growth of bamboo—and, more broadly, how monocots regulate rapid stem elongation. The multi-omics resources (including an interactive web atlas: https://db.cngb.org/stomics/datasets/STDS0000377) offer a foundation for improving crop productivity and developing sustainable biomaterials.

Paper: Qin N, Liu X, Li S, Sun L, Chen C, et al. Single-nucleus and spatial transcriptomics reveal the cell populations of intercalary meristems in bamboo. PNAS 2025;122(51):e2511701122. DOI: 10.1073/pnas.2511701122

Exploring Antarctic Krill Mitogenomes: Insights into Genetic Diversity and Population Dynamics

Tue, 29 Apr 2025 18:00:00 +0800

Antarctic krill (Euphausia superba), a keystone species in the Southern Ocean ecosystem, plays a pivotal role in global marine biodiversity and biogeochemical cycles. In our recent study, we leveraged previously published whole-genome sequencing data of Antarctic krill to conduct a deeper analysis of mitochondrial genomes, shedding light on population evolution and genetic selection pressures.

Key Findings

High-Quality Mitogenome Assembly:
Using PacBio long-read sequencing technology, we assembled the complete mitochondrial genome of Antarctic krill, spanning 18,926 bp with a notably large control region (CR) of 3,952 bp. The CR includes a 2,289 bp tandem repeat, highlighting the advantages of long-read sequencing in resolving complex genomic regions.
NUMTs and Mitogenome Diversity:
Our analysis identified 900 nuclear-mitochondrial DNA segments (NUMTs) in the krill nuclear genome, totaling 2.79 Mb. These NUMTs provide insights into the dynamic integration of mitochondrial DNA into nuclear genomes during and after speciation events. Additionally, we constructed a dataset of 80 krill mitogenomes, revealing substantial mitochondrial diversity and high levels of genetic connectivity across geographically distinct populations in the Southern Ocean.
Population Evolution and Demographic History:
Haplotype network analysis and demographic reconstructions suggest a recent population expansion, likely driven by favorable environmental conditions during the late Pleistocene. Our study also revealed evidence of purifying selection across all 13 mitochondrial protein-coding genes, emphasizing the evolutionary constraint to maintain mitochondrial function under extreme conditions.

Reflections and Comments

This project forms part of the PhD research undertaken by Shuai Sun, one of my doctoral students and a vital member of XinLab. Shuai has contributed significantly to various projects involving crop population genomics and marine species, publishing multiple papers in these fields. This particular study represents a focused effort to analyze mitochondrial genomes and uncover evolutionary insights from mutations and selection pressures within krill populations.

As a mentor, I was impressed by Shuai’s dedication and meticulous approach to this research. Leveraging previously published Antarctic krill genomic data, Shuai conducted an in-depth exploration of mitochondrial genes to reveal their evolutionary dynamics and functional significance. These findings not only advance our understanding of krill population biology but also highlight the importance of integrative genomics for marine species conservation.

Conclusion

Our study provides valuable insights into the mitochondrial genomic landscape of Antarctic krill, offering new perspectives on population genetics and evolutionary history. By combining high-quality genomic data with advanced bioinformatics approaches, we have established a foundational resource for krill conservation and management in the Southern Ocean. This work underscores the critical role of mitochondrial research in addressing broader ecological and evolutionary questions.

探索南极磷虾线粒体基因组：遗传多样性与种群动态的洞见

Tue, 29 Apr 2025 18:00:00 +0800

南极磷虾（Euphausia superba）是南大洋生态系统中的关键物种，在全球海洋生物多样性和生物地球化学循环中发挥着核心作用。在我们最近的研究中，我们利用此前发表的南极磷虾全基因组测序数据对线粒体基因组进行了更深入的分析，揭示了种群演化和遗传选择压力。

主要发现

高质量的线粒体基因组组装： 利用 PacBio 长读长测序技术，我们组装了南极磷虾的完整线粒体基因组，跨度 18,926 bp，其中包含一个显著较大的控制区（CR），达 3,952 bp。该控制区包含一个 2,289 bp 的串联重复序列，凸显了长读长测序在解析复杂基因组区域方面的优势。
NUMT 与线粒体基因组多样性： 我们的分析在磷虾核基因组中鉴定了 900 个核线粒体 DNA 片段（NUMT），总计 2.79 Mb。这些 NUMT 为线粒体 DNA 在物种形成事件期间和之后动态整合到核基因组中提供了洞见。此外，我们构建了一个包含 80 个磷虾线粒体基因组的数据集，揭示了显著的线粒体多样性以及南大洋地理上不同群体间的高水平遗传连通性。
种群演化与群体历史： 单倍型网络分析和群体历史重建表明，磷虾近期发生了种群扩张，可能由更新世晚期的有利环境条件驱动。我们的研究还揭示了所有 13 个线粒体蛋白质编码基因的纯化选择证据，强调了在极端条件下维持线粒体功能的演化约束。

思考与评论

这个项目是我博士生孙帅博士研究的一部分，他是 XinLab 的重要成员。孙帅在作物群体基因组学和海洋物种等多个项目中做出了重要贡献，在这些领域发表了多篇论文。这项特定研究代表了分析线粒体基因组、从磷虾种群的突变和选择压力中揭示演化洞见的专项努力。

作为导师，孙帅对这项研究的奉献和一丝不苟给我留下了深刻印象。他利用此前发表的南极磷虾基因组数据，对线粒体基因进行了深入探索，以揭示其演化动态和功能意义。这些发现不仅推进了我们对磷虾种群生物学的理解，还凸显了整合基因组学对海洋物种保护的重要性。

结论

我们的研究为南极磷虾的线粒体基因组景观提供了宝贵洞见，为种群遗传学和演化历史提供了新视角。通过将高质量基因组数据与先进的生物信息学方法相结合，我们为南大洋磷虾的保护和管理建立了基础资源。这项工作强调了线粒体研究在解决更广泛生态和演化问题中的关键作用。

Tertiary Lymphoid Organ-like Structures in Carotid Artery Plaques: A Breakthrough in Understanding Plaque Instability

Tue, 29 Apr 2025 13:56:51 +0800

Tertiary lymphoid organ-like structures in human atherosclerosis contribute to plaque instability. Xin Liu, on behalf of the XinLab team and our collaborators at Peking Union Medical College Hospital

Carotid artery plaques are a significant risk factor for atherosclerosis and various cardiovascular diseases. Driven by our passion for applying cutting‐edge genomic technologies to real-world clinical challenges, our team set out to unravel the cellular secrets hidden within these plaques. Using spatiotemporal omics and single‑cell sequencing, our research has revealed a previously unappreciated facet of plaque biology—clusters of immune cells that organize into structures strikingly similar to tertiary lymphoid organs (TLOs), commonly observed in tumor microenvironments.

Uncovering the Immune Landscape of Plaques

Our study employed high‑resolution spatial transcriptomics alongside single‑cell RNA sequencing to create a detailed atlas of the cellular composition within carotid plaques. The spatial data provided crucial context: we observed that in select regions of the plaque, immune cells—chiefly B cells and plasma cells—congregated into organized clusters. These structures bear a resemblance to TLS, suggesting that local immune responses may play a pivotal role in plaque progression and instability.

Further integrative analysis allowed us not only to map these cell assemblies but also to tease apart the key factors and signaling pathways that drive their formation. By combining molecular profiling with rigorous histopathological validation (using H&E staining), our data shows that plaques harboring TLS are more likely to be unstable and associated with adverse clinical symptoms. In other words, the presence of these organized immune cell clusters appears to contribute directly to the risk of subsequent cardiovascular events.

Significance of Our Findings

This discovery is particularly significant—it represents the first time that TLS-like structures have been definitively identified within carotid artery plaques. While similar structures have been observed in other atherosclerosis-related tissues, finding them in carotid plaques opens new avenues for understanding the adaptive immune responses that modulate plaque stability. Molecular evidence from our study suggests that the aggregation of B cells and plasma cells could instigate local inflammatory processes, destabilizing the plaque and thereby heightening the risk of clinical events.

Our work not only deepens our understanding of the immune system’s role in atherosclerosis but also uncovers new therapeutic targets. By pinpointing the molecular drivers of TLS formation within plaques, we pave the way for the development of interventions designed to stabilize these high-risk lesions, potentially preventing strokes and other cardiovascular complications.

A Collaborative Milestone

This study marks a major milestone in our research efforts. It was born out of a collaborative synergy between XinLab—a dynamic team led by Xin Liu at BGI—and our colleagues at Peking Union Medical College Hospital, spearheaded by Dr. Bao Liu. Significant contributions from Zhichao Lai, Deqiang Kong, Yue Wang, Qingsong Du, Ziqing Deng, and others exemplify the spirit of teamwork that drives breakthroughs in human disease research. For more information about our lab’s work, please visit www.xgenome.cn and our GitHub page liuxin-genomics.github.io.

Reflections on the Journey

No discovery, however groundbreaking, comes easily. Reflecting on the peer-review journey for this work, I recall a time of grueling scrutiny and intense revision. At moments, it felt like the hurdles were insurmountable; yet, the challenge was also deeply invigorating. In retrospect, every piece of feedback pushed us to refine our analyses and strengthen our conclusions. I find it fascinating how a rigorous review process ultimately enriches research—it shaped our study into something even more compelling and robust.

I am particularly grateful to Reviewer Klaus Ley, who not only provided incisive comments but also authored a thoughtful commentary on our work. His summary, available here, offers a distillation of our findings and an appreciation of their clinical implications. Such insights remind me that science, much like the fabled allegories of transformation, involves a process of refinement—a journey reminiscent of the Chinese fable of Sun Wukong being tempered in Laozi’s alchemy furnace until, in a dramatic reversal, the latent power bursts forth in unexpected ways.

Looking Ahead

Our discovery of TLS-like structures in carotid plaques is only the beginning. It not only underscores the critical role of local immune dynamics in cardiovascular disease but also opens exciting avenues for therapeutic intervention. XinLab remains dedicated to leveraging advanced genomic technologies in our quest to decode complex human diseases. I look forward to sharing more details about our ongoing research and the fascinating lessons learned from our continued exploration of the immune microenvironment in atherosclerosis.

We hope you find our journey as inspiring as we do. Stay tuned for more updates from XinLab, where cutting-edge genomics meets impactful discovery.

颈动脉斑块中的三级淋巴结构：理解斑块不稳定性的突破

Tue, 29 Apr 2025 13:56:51 +0800

人类动脉粥样硬化中的三级淋巴结构样结构导致斑块不稳定。刘心，代表 XinLab 团队及我们在北京协和医院的合作者

颈动脉斑块是动脉粥样硬化和各种心血管疾病的重要风险因素。 出于将前沿基因组技术应用于现实临床挑战的热情，我们的团队着手揭示这些斑块中隐藏的细胞秘密。利用时空组学和单细胞测序，我们的研究揭示了斑块生物学中一个此前未被认识的面貌——免疫细胞聚集成与肿瘤微环境中常见的三级淋巴结构（TLO）惊人相似的结构。

揭示斑块的免疫景观

我们的研究采用高分辨率空间转录组学结合单细胞 RNA 测序，创建了颈动脉斑块内细胞组成的详细图谱。空间数据提供了关键背景：我们观察到，在斑块的特定区域，免疫细胞——主要是 B 细胞和浆细胞——聚集成有组织的簇。这些结构与 TLS 相似，提示局部免疫反应可能在斑块进展和不稳定性中发挥关键作用。

进一步的整合分析不仅使我们能够绘制这些细胞聚集，还厘清了驱动其形成的关键因素和信号通路。通过将分子分析（使用 H&E 染色）与严格的病理学验证相结合，我们的数据表明，含有 TLS 的斑块更可能不稳定，并与不良临床症状相关。换言之，这些有组织的免疫细胞簇的存在似乎直接增加了后续心血管事件的风险。

我们发现的意义

这一发现尤其重要——这是首次在颈动脉斑块中明确鉴定出 TLS 样结构。虽然在动脉粥样硬化相关组织中也观察到类似结构，但在颈动脉斑块中发现它们为理解调节斑块稳定性的适应性免疫反应开辟了新途径。我们研究中的分子证据表明，B 细胞和浆细胞的聚集可能引发局部炎症过程，使斑块不稳定，从而增加临床事件的风险。

我们的工作不仅加深了对免疫系统在动脉粥样硬化中作用的理解，还发现了新的治疗靶点。通过定位斑块内 TLS 形成的分子驱动因素，我们为开发旨在稳定这些高危病变的干预措施铺平了道路，可能预防中风和其他心血管并发症。

合作的里程碑

这项研究是我们研究工作中的重要里程碑。它诞生于 XinLab（华大刘心领导的充满活力的团队）与北京协和医院（由刘宝/刘昌伟博士牵头）同事之间的协同合作。赖智超、孔德强、王月、杜青松、邓子清等人的重要贡献体现了推动人类疾病研究突破的团队精神。关于我们实验室工作的更多信息，请访问 www.xgenome.cn 和我们的 GitHub 页面 liuxin-genomics.github.io。

历程的思考

没有任何发现，无论多么具有开创性，是轻易得来的。回顾这项工作的同行评审历程，我想起了一段艰辛的审查和密集修改的时期。有时感觉障碍无法逾越；然而，挑战也令人深感振奋。回顾起来，每一条反馈都推动我们完善分析、加强结论。我发现严格的评审过程最终如何丰富研究——它把我们的研究塑造成更有说服力、更稳健的作品。

我特别感谢审稿人 Klaus Ley，他不仅提供了精辟的评论，还为我们撰写了深思熟虑的评论文章。他的总结可在此处获取，浓缩了我们的发现并评价了其临床意义。这样的洞见提醒我，科学就像传说中的蜕变寓言一样，涉及一个锤炼的过程——一段让人想起中国寓言中孙悟空在太上老君炼丹炉中经受淬炼，直到在戏剧性的逆转中，潜在的力量以意想不到的方式迸发出来的旅程。

展望未来

我们在颈动脉斑块中发现 TLS 样结构只是开始。它不仅强调了局部免疫动态在心血管疾病中的关键作用，还为治疗干预开辟了令人兴奋的途径。XinLab 仍致力于利用先进的基因组技术破译复杂的人类疾病。我期待分享我们正在进行的研究的更多细节，以及我们从持续探索动脉粥样硬化免疫微环境中获得的宝贵经验。

我们希望您能像我们一样从这段旅程中获得启发。敬请关注 XinLab 的更多更新，在这里，前沿基因组学与有影响力的发现相遇。