Publication文章
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01
Long-term in vivo CRISPR/Cas9 gene editing in liver triggers host immunity and clonal mutations in DNA damage response genes beyond off-target effects
Using the mouse liver as an in vivo model, this letter evaluates the long-term safety of CRISPR/Cas9 genome editing and shows that, beyond off-target effects, prolonged SaCas9 editing also triggers host immune responses and accumulates clonal mutations in DNA damage response genes.
该文以小鼠肝脏为体内模型评估长期 CRISPR/Cas9 基因编辑的安全性，发现除脱靶效应外，长期 SaCas9 编辑还会引发宿主免疫反应，并在 DNA 损伤应答相关基因中产生克隆突变。
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02
Longitudinal lineage tracing reveals early clonal attrition during Drosophila midgut aging
Cited by 1被引 1Longitudinal lineage tracing of the adult Drosophila midgut using an enhanced SMALT system shows that clonal diversity peaks immediately after eclosion and then declines earlier than expected, accompanied by a reduced effective population size. Intestinal stem-cell lineages arising in the first 10 days post-eclosion sustain clonal dominance during aging—a single lineage can comprise over 63% of sampled cells by day 63—and Bayesian survival modelling plus a graph neural network prospectively predict clone survival and structural evolution.
基于改进的 SMALT 系统对成年果蝇中肠进行纵向细胞谱系追踪，发现克隆多样性在羽化后即刻达峰并早于预期开始下降、有效群体大小减小；羽化后 10 天内出现的肠道干细胞谱系在衰老过程中持续占据优势（第 63 天时单一谱系可占采样细胞的 63% 以上），并结合贝叶斯生存模型与图神经网络前瞻性预测了克隆的存续与结构演化。
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03
A comprehensive single-cell atlas of monoallelic expression across various tissues in zebrafish
Using reciprocal crosses between divergent zebrafish strains, whole-genome sequencing and single-cell RNA sequencing, we build a single-cell atlas of allelic expression across 50,819 cells and 37 cell types, identifying 738 monoallelically expressed (MAE) genes and revealing that MAE is widespread and dynamic during vertebrate development and contributes to tissue specialization.
本文结合遗传距离较远的斑马鱼品系正反交、全基因组测序与单细胞 RNA 测序，在 50,819 个细胞、37 种细胞类型中构建了等位基因表达图谱，鉴定出 738 个单等位表达（MAE）基因，揭示 MAE 在脊椎动物发育中广泛而动态，并参与组织特化与调控多样性。
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04
Polyclonal-to-monoclonal transition in colorectal precancerous evolution
Cited by 71被引 71Using base-editor DNA barcoding to build single-cell phylogenies in mouse intestinal tumour models and validating them in human sporadic colorectal polyps, we find that precancerous lesions are often founded polyclonally by multiple lineages and support a 'polyclonal-to-monoclonal transition' model in which monoclonal lesions represent a later stage.
本文利用碱基编辑器 DNA 条形码在小鼠肠肿瘤模型中绘制单细胞系统发育树，并在人类散发性结直肠息肉中加以验证，发现癌前病灶常由多个谱系多克隆奠基，并支持“多克隆向单克隆转变”的模型，其中单克隆病灶代表更晚期的阶段。
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05
Achieving single-cell-resolution lineage tracing in zebrafish by continuous barcoding mutations during embryogenesis
Cited by 9被引 9Applying the SMALT system to zebrafish, we record a median of 14 substitution mutations per 1-kb barcode in one-day post-fertilization embryos and reconstruct cell lineage trees with hundreds of internal nodes (median bootstrap support 99%), showing that regenerated fin cells mainly originate from the same part of the fin and confirming the stability of the germ-cell pool and its early separation from somatic lineages.
本文将 SMALT 系统应用于斑马鱼，在受精后一天胚胎的 1 kb 条形码上平均记录 14 个替换突变，重建出内部节点达数百个、自举支持率中位数为 99% 的细胞谱系树，揭示再生鳍细胞主要来自同一部位，并证实生殖细胞库的稳定性及其与体细胞谱系的早期分离。
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06
Variation in cancer risk between organs can not be explained by the degree of somatic clonal expansion
Cited by 7被引 7Quantifying somatic clonal expansion across nine human organs, we find that its degree varies among organs but is consistent among individuals and is not significantly correlated with lifetime cancer risk, suggesting that somatic clonal expansion in normal tissues is an evolutionary process distinct from carcinogenesis.
本文定量评估了九种人体器官的体细胞克隆扩增程度，发现其因器官而异、在个体间一致，且与终生癌症风险并无显著相关，提示正常组织中的体细胞克隆扩增是与癌变不同的一种独立演化过程。
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07
Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain
Cited by 23被引 23We develop PATTERN, a photoacoustic tomography platform with temporal-encoding reconstruction for non-destructive, high-speed 3D imaging of ex vivo rodent, ferret and non-human primate brains, which can be combined with other whole-brain imaging modalities and transcriptomic analysis for individual-level cross-modal studies.
本文开发了光声断层成像结合时间编码重建（PATTERN）平台，可对啮齿类、雪貂及非人灵长类离体全脑进行无损、高速的三维成像，并能与其他全脑成像模态及转录组分析结合，实现个体水平的跨模态全脑研究。
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08
A statistical method for quantifying progenitor cells reveals incipient cell fate commitments
Cited by 18被引 18We propose TarCA, a statistical method that quantifies progenitor cells without progenitor-specific markers by computing the coalescent probability of two randomly sampled cells in the cell phylogenetic tree; it is validated in nematode, fruit fly and mouse data and used to identify lineage-specific upregulated genes and incipient cell fate commitments in mouse embryos.
本文提出无需祖细胞特异标志物的统计方法 TarCA，通过细胞系统发育树计算同一组织内两随机细胞的溯祖概率来估计祖细胞数目，并在线虫、果蝇和小鼠数据中得到验证，进而识别出小鼠胚胎发育中的谱系特异上调基因与早期细胞命运决定。
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09
Tree of life at two levels: from species to cell
Cited by 2被引 2This perspective parallels species trees with cell trees, reviews recent progress in reconstructing the developmental cell tree of complex multicellular organisms using somatic mutations and cell-tree-based population-genetic modelling, and anticipates the convergence of evolutionary biology with molecular, cellular and developmental biology.
本文以物种树类比细胞树，综述了利用体细胞突变重建复杂多细胞生物发育细胞树的最新进展及基于细胞树的群体遗传建模，并展望生态与演化生物学同分子、细胞与发育生物学的融合。
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10
Mutation signatures inform the natural host of SARS-CoV-2
Cited by 37被引 37By comparing the mutation spectra of SARS-CoV-2 and six related coronaviruses, we find that the pre-outbreak branch is nearly identical to the bat branch RaTG13 (i-score 99.9%) and clearly distinct from the post-outbreak human branch, suggesting a bat host and an unlikely artificial synthesis.
通过比较 SARS-CoV-2 与六种近缘冠状病毒的突变谱，发现疫情前分支的突变谱与蝙蝠宿主分支（如 RaTG13）近乎一致（i-score 99.9%），而与疫情后的人群分支明显不同，提示其自然宿主为蝙蝠，且该病毒不太可能为人工合成。
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11
Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development
Cited by 62被引 62We developed SMALT, a substitution mutation-aided lineage-tracing system that records on average roughly 21 substitution mutations per barcode in early-adult Drosophila cells (effective barcoding space > 10^30), enabling near single-cell-resolution cell phylogenies and reconstruction of developmental cell population dynamics in more than 12 fly organs.
本文开发了基于替换突变的谱系追踪系统 SMALT，在果蝇早期成体细胞中每个条形码平均记录约21 个替换突变（有效编码空间大于 10^30），由此重建了近单细胞分辨率的细胞系统发育树，并解析出 12 个以上器官发育过程中的细胞群体动态。
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12
An instantaneous coalescent method insensitive to population structure
Cited by 6被引 6We propose i-coalescent analysis, a coalescent method insensitive to population structure: the coalescent probability one generation back is independent of population structure, and a phylogenetic tree of sampled alleles can accurately reconstruct the population-size dynamics of highly structured populations.
本文提出对群体结构不敏感的 i-coalescent（瞬时溯祖）方法，证明相邻上一代的溯祖概率与群体结构无关，并可基于取样等位的系统发育树准确重建高度结构化群体的有效群体大小动态。
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13
Drivers of Mating Type Composition in Tetrahymena thermophila
Cited by 9被引 9Using a population-genetics model together with an evolution experiment, we show that the mating-type composition of Tetrahymena thermophila is determined mainly by the ratio of sexual to asexual cell survival and the strength of natural selection, with beneficial mutations driving the fixation of their carrying mating types.
本文通过种群遗传学模型与演化实验，揭示四膜虫（Tetrahymena thermophila）七种交配型的组成动态主要取决于有性/无性细胞存活率之比与自然选择强度，实验群体中携带新发有益突变的交配型受强选择驱动而趋于固定。
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14
Decoupling gene functions from knockout effects by evolutionary analyses
Cited by 7被引 7Using the yeast transcription factor HAP4 as an example, we find that most of a gene's pleiotropic knockout effects are non-heritable and poorly conserved across related yeasts, and are therefore evolutionarily decoupled from the gene's normal function, suggesting a new framework for reverse genetics.
以酵母转录因子 HAP4 为例，发现基因敲除的大多数多效性表达效应在群体中不可遗传、在近缘酵母中不保守，因而在进化上与基因本身的正常功能相脱耦，为反向遗传学分析提出了新框架。
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