本期我們通過PubMed數(shù)據(jù)庫檢索，整理了從2021年8月1日到8月31單細(xì)胞技術(shù)文章共764篇。其中IF (影響因子)大于9分的文章有216篇（文章后面使用表格列出），現(xiàn)選擇其中20篇代表性文章進(jìn)行導(dǎo)讀，詳情如下：
1
英文題目：Molecular phenotyping reveals the identity of Barrett's esophagus and its malignant transition
中文題目：分子表型揭示巴雷特食管的特征及其惡性轉(zhuǎn)變
發(fā)表時間：2021-08-13
發(fā)表雜志：Science
影響因子：47.720
DOI：10.1126/science.abd1449
摘要：人類化生狀態(tài)的起源及其致癌傾向尚不清楚。Barrett食管是一種常見的化生性疾病，會增加食管腺癌的發(fā)病風(fēng)險，其細(xì)胞起源不明。為了解決這個問題，我們從健康和患病供體中采集了跨越胃食管連接處的組織，包括分離食管粘膜下腺。單細(xì)胞轉(zhuǎn)錄組分析、甲基化的計算機(jī)譜系追蹤、開放染色質(zhì)和體細(xì)胞突變分析以及類器官模型的功能研究表明，Barrett食管通過 c-MYC 和 HNF4A 驅(qū)動的轉(zhuǎn)錄程序起源于賁門。此外，我們的數(shù)據(jù)表明，食管腺癌可能源自未分化的Barrett食管細(xì)胞類型，即使在缺乏病理學(xué)上可識別的化生全體的情況下，這也揭示了早期的檢測策略。
2
英文題目：Spatial transcriptomics of planktonic and sessile bacterial populations at single-cell resolution
中文題目：單細(xì)胞分辨率下浮游和固著細(xì)菌種群的空間轉(zhuǎn)錄組學(xué)
發(fā)表時間：2021-08-13
發(fā)表雜志：Science
影響因子：47.720
DOI：10.1126/science.abi4882
摘要：在相關(guān)的時空尺度上捕獲微生物種群的異質(zhì)表型是一項極具挑戰(zhàn)性的工作。在這里，我們介紹了par-seqFISH（平行順序熒光原位雜交），這是一種轉(zhuǎn)錄組成像方法，以單細(xì)胞和分子分辨率記錄微尺度組裝中的基因表達(dá)和空間背景。我們將這種方法應(yīng)用于機(jī)會致病菌銅綠假單胞菌，分析了浮游生物和生物膜培養(yǎng)中數(shù)十種條件下的約60萬個個體。我們鑒定了浮游生物生長期間動態(tài)出現(xiàn)的許多代謝和毒力相關(guān)的轉(zhuǎn)錄狀態(tài)，以及固著種群中高度空間分辨的代謝異質(zhì)性。我們的數(shù)據(jù)顯示，不同的生理狀態(tài)可以共存于幾微米之外的同一生物膜中，這突出了微環(huán)境的重要性。我們的結(jié)果揭示了微生物種群的復(fù)雜動態(tài)，并提供了一種高分辨率研究微生物種群的新方法。
3
英文題目：A clinically applicable integrative molecular classification of meningiomas
中文題目：一種臨床適用的腦膜瘤綜合分子分類方法
發(fā)表時間：2021-08-25
發(fā)表雜志：Nature
影響因子：49.962
DOI：10.1038/s41586-021-03850-3
摘要：腦膜瘤是成人最常見的原發(fā)性顱內(nèi)腫瘤。由于沒有有效的藥物治療，出現(xiàn)癥狀的患者一般采用手術(shù)治療。世界衛(wèi)生組織腫瘤的組織病理學(xué)分級和手術(shù)切除范圍(Simpson分級)與疾病復(fù)發(fā)有關(guān)；然而，它們不能準(zhǔn)確反映所有腦膜瘤的臨床表現(xiàn)。腦膜瘤的分子分類需要可靠地反映腫瘤行為和提供治療信息。在這里，我們通過將DNA體拷貝數(shù)畸變、DNA體點突變、DNA甲基化和信使RNA豐度結(jié)合在一個統(tǒng)一的分析中，介紹了腦膜瘤的四個共有分子組。與現(xiàn)有的分類方案相比，這些分子組更準(zhǔn)確地預(yù)測了臨床結(jié)果。每個分子組都顯示了獨特的原生生物學(xué)特性(免疫原性、良性的NF2野生型、高代謝和增殖) ，為治療選擇提供了依據(jù)。蛋白質(zhì)基因組特征增強(qiáng)了新定義分子組的穩(wěn)健性，并發(fā)現(xiàn)了高度豐富和組特異性的蛋白靶點，我們使用免疫組化進(jìn)行了驗證。單細(xì)胞RNA測序揭示了腦膜瘤個體間的差異，以及腫瘤細(xì)胞內(nèi)表達(dá)程序的差異，這些差異反映了所鑒定的分子組的生物學(xué)特性。
4
英文題目：Clonal dynamics in early human embryogenesis inferred from somatic mutation
中文題目：從體細(xì)胞突變推測人類早期胚胎發(fā)育的隆動力學(xué)
發(fā)表時間：2021-08-25
發(fā)表雜志：Nature
影響因子：49.962
DOI：10.1038/s41586-021-03786-8
摘要：由于在人類胚胎中進(jìn)行研究的挑戰(zhàn)，早期人類胚胎發(fā)生中的細(xì)胞動力學(xué)和命運(yùn)決定在很大程度上仍是未知的。在這里，我們探索了334個單細(xì)胞克隆的全基因組，并針對從7個最近去世的成年人類捐贈者的不同解剖位置獲得的379個塊狀組織的深層序列。使用體細(xì)胞突變作為內(nèi)在條形碼，我們重建了早期細(xì)胞系統(tǒng)發(fā)育，表明在第一次細(xì)胞分裂時內(nèi)源性突變率較高，但在生命后期降低到大約每個細(xì)胞分裂一次；早期細(xì)胞對胚胎本身的貢獻(xiàn)普遍不平等，這是由于早期細(xì)胞瓶頸隨機(jī)地將胚胎內(nèi)的外胚層細(xì)胞擱置。在身體左右兩側(cè)的組織、不同的胚層和特定的解剖部位和器官之間不同程度的早期克隆失衡的例子，出現(xiàn)了一些祖先細(xì)胞，它們將對血液和肝臟中的成體細(xì)胞庫做出實質(zhì)性貢獻(xiàn); 受精卵中存在線粒體DNA異質(zhì)性。我們的方法也為正常體細(xì)胞中與年齡相關(guān)的突變過程和性染色體的丟失提供了見解。綜上所述，本研究為完成人類胚胎發(fā)生中細(xì)胞系統(tǒng)發(fā)育的研究奠定了基礎(chǔ)。
5
英文題目：Whole-body integration of gene expression and single-cell morphology
中文題目：基因表達(dá)和單細(xì)胞形態(tài)的整體整合
發(fā)表時間：2021-08-10
發(fā)表雜志：Cell
影響因子：41.582
DOI：10.1016/j.cell.2021.07.017
摘要：動物的身體是由具有獨特表達(dá)程序的細(xì)胞類型組成的，這些細(xì)胞類型實現(xiàn)了它們獨特的位置、形狀、結(jié)構(gòu)和功能。基于這些特性，細(xì)胞類型組裝成特定的組織和器官。為了系統(tǒng)地探索細(xì)胞類型特異性基因表達(dá)與形態(tài)之間的聯(lián)系，我們將表達(dá)圖譜注冊到圓葉藻的全身電子顯微鏡體積中。細(xì)胞和細(xì)胞核的自動分割識別了主要的細(xì)胞類別，并在基因激活、染色質(zhì)形貌和細(xì)胞核大小之間建立了聯(lián)系。根據(jù)基因表達(dá)將分裂的細(xì)胞聚類顯示出空間上一致的組織。在大腦中，基因定義的神經(jīng)元群與神經(jīng)節(jié)核相匹配，具有一致的投射。除了中間神經(jīng)元外，我們還在海棠菇體中發(fā)現(xiàn)了感覺神經(jīng)分泌細(xì)胞，因此被稱為感覺器官。在分子解剖學(xué)上，它們更類似脊椎動物的端腦。我們提供了一個集成的瀏覽器作為Fiji插件，用于遠(yuǎn)程探索所有可用的多模式數(shù)據(jù)集。
6
英文題目：Single-cell measurement of higher-order 3D genome organization with scSPRITE
中文題目：用scSPRITE進(jìn)行高階3D基因組組織的單細(xì)胞測量
發(fā)表時間：2021-08-23
發(fā)表雜志：Nat Biotechnol
影響因子：54.908
DOI：10.1038/s41587-021-00998-1
摘要：雖然三維(3D)基因組組織是核功能許多方面的核心，但很難在單細(xì)胞水平上測量。為了解決這個問題，我們開發(fā)了“通過標(biāo)簽擴(kuò)展進(jìn)行交互的單細(xì)胞分裂池識別”(scSPRITE)。scSPRITE使用split-and-pool條形碼來標(biāo)記同一細(xì)胞核中的DNA片段及其三維空間排列。由于scSPRITE測量的是多路DNA接觸，它在單個細(xì)胞內(nèi)生成的圖的分辨率比近距離連接更高。我們將scSPRITE應(yīng)用于數(shù)千個小鼠胚胎干細(xì)胞，檢測到已知的基因組結(jié)構(gòu)，包括染色體區(qū)域、活性和非活性區(qū)、拓?fù)潢P(guān)聯(lián)域(TADs)以及圍繞不同核體組織的長程染色體間結(jié)構(gòu)。我們觀察到這些結(jié)構(gòu)在群體中表現(xiàn)出不同水平的異質(zhì)性，TADs代表了細(xì)胞中基因組組織的動態(tài)單位。我們期望scSPRITE將成為研究異質(zhì)群體基因組結(jié)構(gòu)的關(guān)鍵工具。
7
英文題目：Aged skeletal stem cells generate an inflammatory degenerative niche
中文題目：老化的骨骼干細(xì)胞產(chǎn)生炎癥性退行性生態(tài)位
發(fā)表雜志：nature
發(fā)表時間：2021-8-11
影響因子：49.962
DOI：10.1038/s41586-021-03795-7
摘要：衰老和疾病期間骨骼完整性的喪失與成骨細(xì)胞和破骨細(xì)胞相反作用的不平衡有關(guān)。在這里，我們表明，小鼠骨骼干細(xì)胞（SSCs）的固有老化改變了骨髓生態(tài)位中的信號傳導(dǎo)，扭曲了骨骼和血液譜系的分化，導(dǎo)致脆弱的骨骼再生不良。從功能上講，衰老的SSCs骨和軟骨形成潛能降低，但產(chǎn)生更多的基質(zhì)譜系，表達(dá)高水平的促炎癥和促吸收細(xì)胞因子。單細(xì)胞RNA測序研究將功能喪失與衰老小鼠SSCs轉(zhuǎn)錄組多樣性減少聯(lián)系起來，從而有助于骨髓生態(tài)位的轉(zhuǎn)化。通過異慢性副生性或年輕造血干細(xì)胞的系統(tǒng)重建暴露于年輕循環(huán)中，不會逆轉(zhuǎn)老年SSCs骨軟骨生成活性的降低，也不會改善老年小鼠的骨量或骨骼愈合參數(shù)。相反，衰老的SSCs譜系通過造血干細(xì)胞和祖細(xì)胞促進(jìn)破骨細(xì)胞活性和髓樣變斜，表明SSCs的老化是造血老化的驅(qū)動因素。老年小鼠骨再生不足只能通過局部應(yīng)用BMP2和CSF1拮抗劑的組合治療恢復(fù)到年輕水平，從而重新激活老年SSCs，同時清除炎癥、促破骨細(xì)胞環(huán)境。我們的研究結(jié)果為骨骼老化的復(fù)雜、多因素機(jī)制提供了機(jī)制上的見解，并為老年骨骼系統(tǒng)的再生提供了前景。
8
英文題目：Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche
中文題目：定量譜系分析確定肝胰膽管祖細(xì)胞生態(tài)位
發(fā)表雜志：nature
發(fā)表時間：2021-8-25
影響因子：49.962
DOI：10.1038/s41586-021-03844-1
摘要：基于單細(xì)胞的研究揭示了干細(xì)胞和祖細(xì)胞間的巨大細(xì)胞異質(zhì)性，表明在器官發(fā)生過程中，細(xì)胞在不同的譜系承諾狀態(tài)和顯著的可塑性程度下混合的持續(xù)分化軌跡。肝-胰-膽管器官系統(tǒng)依賴于一個小型內(nèi)胚層祖細(xì)胞室，產(chǎn)生多種不同的成人組織，包括肝臟、胰腺、膽囊和肝外膽管。小鼠胚胎中各種發(fā)育信號的實驗操作強(qiáng)調(diào)了這一胚胎區(qū)域的重要細(xì)胞可塑性。這反映在人類遺傳綜合征的存在以及肝臟、胰腺和膽囊中具有多器官表型的先天性畸形中。然而，導(dǎo)致內(nèi)胚層祖細(xì)胞室分離為肝臟、膽道和胰腺結(jié)構(gòu)的確切譜系層次和事件序列尚未確定。在這里，我們將計算建模方法與遺傳譜系追蹤相結(jié)合，以準(zhǔn)確地重建肝-胰-膽管譜系樹。我們發(fā)現(xiàn)肝-胰-膽管器官雛形中存在一個多能祖細(xì)胞亞群，不僅為胰腺和膽囊提供細(xì)胞，而且為肝臟提供細(xì)胞。此外，利用單細(xì)胞RNA測序和功能性實驗，我們定義了一個特殊的生態(tài)位，在發(fā)育過程中長時間以多能狀態(tài)支持該亞群。這些發(fā)現(xiàn)共同表明肝-胰-膽管發(fā)育的持續(xù)可塑性，這也可能解釋了肝臟快速擴(kuò)張同時抑制胰膽管生長的原因。
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英文題目：Spatial omics and multiplexed imaging to explore cancer biology
中文題目：空間組學(xué)和多重成像探索癌癥生物學(xué)。
發(fā)表時間：2021-08-02
發(fā)表雜志：Nature Methods
影響因子：28.547
DOI：10.1038/s41592-021-01203-6
摘要：了解腫瘤內(nèi)異質(zhì)性——腫瘤內(nèi)部細(xì)胞間的分子變異——有望解決癌癥生物學(xué)中的突出問題，提高對特定癌癥亞型的診斷和治療。單細(xì)胞分析，特別是RNA測序和其他基因組學(xué)模式，在揭示與腫瘤生長、轉(zhuǎn)移和耐藥性相關(guān)的新型生物標(biāo)記物和分子調(diào)節(jié)劑方面具有革命性。然而，這些方法無法提供完整的腫瘤生物學(xué)圖像，因為關(guān)于腫瘤微環(huán)境中細(xì)胞位置的信息丟失了。利用多重?zé)晒?、DNA、RNA同位素標(biāo)記的新技術(shù)，可以在其天然空間環(huán)境內(nèi)檢測數(shù)以萬計的癌癥亞克隆或分子生物標(biāo)志物。這些技術(shù)的迅速發(fā)展，以及多組學(xué)數(shù)據(jù)整合的方法，有望使人們更全面地了解單個腫瘤內(nèi)部和之間的細(xì)胞間變異。在這里，我們提供了現(xiàn)有狀態(tài)和未來的空間技術(shù)視角，該技術(shù)預(yù)期推動下一代癌癥研究和診斷及治療策略。
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英文題目：Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution
中文題目：單細(xì)胞分辨率下發(fā)育中人類大腦皮層的染色質(zhì)和基因調(diào)控動態(tài)變化
發(fā)表時間：2021-08-11
發(fā)表雜志：Cell
影響因子：41.582
DOI：10.1016/j.cell.2021.07.039
摘要：大腦皮層發(fā)育的遺傳干擾可導(dǎo)致神經(jīng)發(fā)育疾病，包括自閉癥譜系障礙（ASD）。為了確定對皮層發(fā)育至關(guān)重要的基因組域，研究人員繪制了基因調(diào)控元件的活性圖譜，生成了一個獨立和聯(lián)合的基因表達(dá)和染色質(zhì)可及性的單細(xì)胞圖譜。這揭示了關(guān)鍵轉(zhuǎn)錄因子（TFs）在幾乎連續(xù)分化軌跡中的基因調(diào)控浪潮，區(qū)分了膠質(zhì)細(xì)胞系的表達(dá)程序，并確定了決定細(xì)胞系的TFs，這些TFs在連接的基因調(diào)控元件和表達(dá)水平之間表現(xiàn)出強(qiáng)烈的相關(guān)性。這些高度關(guān)聯(lián)的基因在早期分化的細(xì)胞中采用了活躍的染色質(zhì)狀態(tài)，與譜系定型一致。堿基分辨率的神經(jīng)網(wǎng)絡(luò)模型確定了非編碼突變在自閉癥譜系障礙個體隊列中的強(qiáng)烈細(xì)胞類型特異性富集，并確定了經(jīng)常被破壞的TF結(jié)合位點。這種方法說明了細(xì)胞類型特異性圖譜如何能夠提供對人類發(fā)育和疾病控制程序的洞察。
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英文題目：Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)
中文題目：通過克隆型鄰域圖分析(CoNGA)整合T細(xì)胞受體序列和轉(zhuǎn)錄譜
發(fā)表時間：2021-08-23
發(fā)表雜志：Nat Biotechnol
影響因子：54.908
DOI：10.1038/s41587-021-00989-2
摘要：T細(xì)胞克隆型(由T細(xì)胞受體(TCR)序列定義)與表型(反映在基因表達(dá)(GEX)譜、表面蛋白表達(dá)和多肽:主要組織相容性復(fù)合體結(jié)合)之間的聯(lián)系，可以揭示除克隆相關(guān)細(xì)胞共享的特征之外的功能關(guān)系。在此，我們提出了克隆型鄰域圖分析(CoNGA)，一種通過對GEX和TCR相似性圖的統(tǒng)計分析來識別GEX輪廓和TCR序列之間的相關(guān)性的圖論方法。利用CoNGA，我們發(fā)現(xiàn)了TCR序列和GEX譜之間的關(guān)聯(lián)，其中包括之前未描述的人類循環(huán)CD8+T細(xì)胞的“自然淋巴細(xì)胞”群體和一組胸腺細(xì)胞分化的TCR序列決定因素。這些例子表明，CoNGA可能有助于闡明大型、異質(zhì)性、單細(xì)胞數(shù)據(jù)集中TCR序列和T細(xì)胞表型之間的復(fù)雜關(guān)系。
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英文題目：SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data
中文題目：SnapHiC:從單細(xì)胞Hi-C數(shù)據(jù)中識別染色質(zhì)循環(huán)的計算管道
發(fā)表時間：2021-08-26
發(fā)表雜志：Nat Methods
影響因子：28.547
DOI：10.1038/s41592-021-01231-2
摘要：單細(xì)胞Hi-C(scHi-C)分析已經(jīng)越來越多地用于繪制不同組織環(huán)境中的染色質(zhì)結(jié)構(gòu)，但從scHi-C數(shù)據(jù)中以高分辨率定義染色質(zhì)環(huán)的計算工具仍然缺乏。在這里，我們描述了Hi-C的單核分析管道(SnapHiC)，這是一種可以從scHi-C數(shù)據(jù)中以高分辨率和準(zhǔn)確性識別染色質(zhì)環(huán)的方法。利用來自742個小鼠胚胎干細(xì)胞的scHi-C數(shù)據(jù)，我們將SnapHiC與一些用于繪制染色質(zhì)環(huán)和大量Hi-C相互作用的計算工具進(jìn)行基準(zhǔn)測試。我們通過分析來自2869個人類前額葉皮質(zhì)細(xì)胞的單核甲基-3C-seq數(shù)據(jù)，進(jìn)一步證明它的用途，這些數(shù)據(jù)揭示了細(xì)胞類型特異性的染色質(zhì)環(huán)，并預(yù)測了與神經(jīng)精神疾病相關(guān)的非編碼序列變異的假定靶基因。我們的研究結(jié)果表明，SnapHiC有助于對復(fù)雜組織中細(xì)胞類型特異性染色質(zhì)結(jié)構(gòu)和基因調(diào)控程序的分析。
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英文題目：Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
中文題目：上呼吸道預(yù)先激活的抗病毒先天免疫控制了兒童早期SARS-CoV-2感染
發(fā)表時間：2021-08-18
發(fā)表雜志：Nat Biotechnol
影響因子：54.908
DOI：10.1038/s41587-021-01037-9
摘要：與成人相比，兒童的嚴(yán)重急性呼吸系統(tǒng)綜合征冠狀病毒2(SARS-CoV-2)感染率降低，患2019年嚴(yán)重冠狀病毒病的風(fēng)險大大降低。然而，在較年輕的年齡組中提供保護(hù)的分子機(jī)制尚不清楚。在這里，我們描述了sars-cov-2陰性(n=18)和年齡匹配的sars-cov-2陽性(n=24)兒童和相應(yīng)的成人樣本(n=44)呼吸道的單細(xì)胞轉(zhuǎn)錄情況，年齡范圍從4周至77歲。在上氣道上皮細(xì)胞、巨噬細(xì)胞和樹突狀細(xì)胞中，兒童表現(xiàn)出更高的相關(guān)模式識別受體如MDA5 (IFIH1)和RIG-I (DDX58)的基礎(chǔ)表達(dá)，導(dǎo)致兒童在感染SARS-CoV-2時比成人更強(qiáng)的先天抗病毒反應(yīng)。我們進(jìn)一步檢測到不同的免疫細(xì)胞亞群，包括KLRC1(NKG2A)+細(xì)胞毒性T細(xì)胞和主要發(fā)生在兒童的具有記憶表型的CD8+ T細(xì)胞群。我們的研究提供了證據(jù)，表明兒童的氣道免疫細(xì)胞為病毒感知做好了準(zhǔn)備，導(dǎo)致對SARS-CoV-2感染的早期先天抗病毒反應(yīng)比成人更強(qiáng)。
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英文題目：SCITO-seq: single-cell combinatorial indexed cytometry sequencing
中文題目：SCITO-seq:單細(xì)胞組合索引細(xì)胞計數(shù)測序
發(fā)表時間：2021-08-05
發(fā)表雜志：Nat Methods
影響因子：28.547
DOI：10.1038/s41592-021-01222-3
摘要：用于標(biāo)記細(xì)胞表面分子的dna條形碼抗體的開發(fā)使得使用基于液滴的單細(xì)胞測序(dsc-seq)同時分析數(shù)千個細(xì)胞的蛋白質(zhì)豐度成為可能。與流式和大規(guī)模細(xì)胞檢測技術(shù)相比，目前基于dsc-seq的工作流每細(xì)胞的高成本妨礙了它們在臨床應(yīng)用和大規(guī)模合并篩選中的使用。在這里，我們介紹了SCITO-seq，這是一個使用夾板寡核苷酸（寡核苷酸）的工作流程，使用商業(yè)微流體對每次反應(yīng)來自超過105個細(xì)胞的dna條形碼抗體進(jìn)行組合索引的dsc-seq。通過將樣本條形碼編碼為夾板寡核苷酸，我們證明了多路SCITO-seq產(chǎn)生可重復(fù)的細(xì)胞組成和表面蛋白表達(dá)估計，與大規(guī)模細(xì)胞術(shù)的估計相當(dāng)。我們進(jìn)一步展示了兩種改進(jìn)的夾板寡核苷酸設(shè)計，它們擴(kuò)展了SCITO-seq，以實現(xiàn)與商業(yè)dna條形碼抗體的兼容性，并同時對來自同一細(xì)胞的轉(zhuǎn)錄組和表面蛋白進(jìn)行表達(dá)譜。這些結(jié)果表明，scto -seq是一個靈活的、超高通量的單細(xì)胞蛋白測序和多模態(tài)分析平臺。
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英文題目：Mapping single-cell data to reference atlases by transfer learning
中文題目：通過轉(zhuǎn)移學(xué)習(xí)將單細(xì)胞數(shù)據(jù)映射到參考圖譜
發(fā)表時間：2021-08-30
發(fā)表雜志：Nat Biotechnol
影響因子：54.908
DOI：10.1038/s41587-021-01001-7
摘要：大型單細(xì)胞圖譜現(xiàn)在被常規(guī)生成，作為分析小規(guī)模研究的參考。然而，由于數(shù)據(jù)集之間的批處理效應(yīng)、計算資源的可用性有限和對原始數(shù)據(jù)的共享限制，從參考數(shù)據(jù)中學(xué)習(xí)變得復(fù)雜。在這里，我們介紹了一種深度學(xué)習(xí)策略，用于映射一個稱為單細(xì)胞架構(gòu)手術(shù)(scArches)的參考之上的查詢數(shù)據(jù)集。scArches使用傳輸學(xué)習(xí)和參數(shù)優(yōu)化，在不共享原始數(shù)據(jù)的情況下實現(xiàn)新數(shù)據(jù)集的高效、分散、迭代的參考構(gòu)建和上下文化，而不共享原始數(shù)據(jù)。利用來自小鼠大腦、胰腺、免疫和全生物體圖譜的例子，我們表明，盡管scArchs使用了比從頭整合少四個數(shù)量級的參數(shù)，但在去除批效應(yīng)的同時保留了生物狀態(tài)信息。最后，scArches保留了2019冠狀病毒病(COVID-19)的疾病變異，當(dāng)映射到健康參考時，可以發(fā)現(xiàn)特定疾病的細(xì)胞狀態(tài)。scarch將通過迭代構(gòu)建、更新、共享和有效使用參考地圖集來促進(jìn)合作項目。
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英文題目：Reinforcing neuron extraction and spike inference in calcium imaging using deep self-supervised denoising
中文題目：利用深度自監(jiān)督去噪在鈣成像中的神經(jīng)元提取和峰推理
發(fā)表時間：2021-08-16
發(fā)表雜志：Nat Methods
影響因子：28.547
DOI：10.1038/s41592-021-01225-0
摘要：鈣成像通過提供了一種以單細(xì)胞分辨率監(jiān)測神經(jīng)回路活動的方法，改變了神經(jīng)科學(xué)研究。然而，鈣成像本質(zhì)上容易受到檢測噪聲的影響，特別是在高幀率或低激發(fā)劑量的成像時。在這里，我們開發(fā)了DeepCAD，一種用于鈣成像數(shù)據(jù)時空增強(qiáng)的自監(jiān)督深度學(xué)習(xí)方法，不需要任何高信噪比(SNR)觀測。DeepCAD抑制了檢測噪聲，將信噪比提高了十倍以上，提高了神經(jīng)元提取和尖峰推斷的準(zhǔn)確性，促進(jìn)了神經(jīng)回路的功能分析。
17
英文題目：Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics
中文題目：通過單細(xì)胞空間轉(zhuǎn)錄組學(xué)鑒定胎兒肝臟中的HSC/MPP擴(kuò)增單位
發(fā)表時間：2021-08-02
發(fā)表雜志：Cell research
影響因子：25.617
DOI：10.1038/s41422-021-00540-7
摘要：造血干細(xì)胞和多能祖細(xì)胞（HSC/MPP）在其自然生態(tài)位內(nèi)擴(kuò)增的細(xì)胞和分子機(jī)制的有限知識阻礙了基于干細(xì)胞的血液惡性腫瘤治療的應(yīng)用。在此，我們構(gòu)建了小鼠胎肝（FL）的時空轉(zhuǎn)錄組圖譜，作為新調(diào)控機(jī)制的假設(shè)生成和后續(xù)實驗驗證的平臺。單細(xì)胞轉(zhuǎn)錄組學(xué)顯示三個轉(zhuǎn)錄異質(zhì)性HSC/MPP亞群，其中一個富含CD93的亞群表現(xiàn)出增強(qiáng)的干細(xì)胞特性。此外，通過單細(xì)胞和空間轉(zhuǎn)錄組學(xué)的綜合分析，我們發(fā)現(xiàn)了新的HSC/MPP“口袋狀”單元（HSC PLUS），由小生境細(xì)胞（成肝細(xì)胞、基質(zhì)細(xì)胞、內(nèi)皮細(xì)胞和巨噬細(xì)胞）組成，富含生長因子。出人意料的是，巨噬細(xì)胞在HSC PLUS中的富集程度為11倍。在功能上，巨噬細(xì)胞HSC/MPP共培養(yǎng)試驗和候選分子試驗分別驗證了巨噬細(xì)胞和生長因子（MDK、PTN和IGFBP5）在HSC/MPP擴(kuò)增中的支持作用。最后，跨物種分析和功能驗證表明，小鼠和人類FL-HSC/MPP之間存在保守的細(xì)胞間相互作用和擴(kuò)增機(jī)制，但轉(zhuǎn)錄組特征不同。綜上所述，這些結(jié)果為理解FL中HSC/MPP的發(fā)展提供了必要的資源，并對功能性HSC/MPP的體外擴(kuò)增提供了新的見解。
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英文題目：Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level
中文題目：大腸癌肝轉(zhuǎn)移單細(xì)胞水平的時空免疫景觀
發(fā)表時間：2021-08-20
發(fā)表雜志：Cancer discovery
影響因子：39.397
DOI：10.1158/2159-8290.CD-21-0316
摘要：肝轉(zhuǎn)移是導(dǎo)致結(jié)直腸癌死亡的主要原因，表現(xiàn)出高度異質(zhì)性和抑制性的免疫微環(huán)境。在這里，我們使用單細(xì)胞RNA測序和空間轉(zhuǎn)錄組學(xué)對97個匹配樣本進(jìn)行測序。引人注目的是，轉(zhuǎn)移性微環(huán)境經(jīng)歷了免疫抑制細(xì)胞如MRC1+CCL18+M2樣巨噬細(xì)胞的顯著空間重編程。我們進(jìn)一步開發(fā)了SCM代謝，一種用于量化單細(xì)胞代謝的計算管道，并觀察到這些巨噬細(xì)胞具有增強(qiáng)的代謝活性。有趣的是，新輔助化療可以阻斷這種狀態(tài)，并在反應(yīng)性患者中恢復(fù)抗腫瘤免疫平衡，而非反應(yīng)性患者惡化為更具抑制性的患者。我們的工作描述了轉(zhuǎn)移的免疫進(jìn)化，并揭示了腫瘤對新輔助化療的反應(yīng)。
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英文題目：Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing
中文題目：通過單細(xì)胞RNA測序定義發(fā)育中和成人腎臟中的多種細(xì)胞類型
發(fā)表時間：2021-08-11
發(fā)表雜志：NPJ Regen Med
影響因子：10.364
DOI：10.1038/s41536-021-00156-w
摘要：就細(xì)胞類型的多樣性而言，腎臟是最復(fù)雜的器官之一。人類腎臟的細(xì)胞復(fù)雜性尚未完全解開，而且多種祖細(xì)胞池和分化途徑的存在，使這一挑戰(zhàn)變得更加復(fù)雜。由于缺乏全面圖像的研究以及在物種之間轉(zhuǎn)換發(fā)現(xiàn)的挑戰(zhàn)，研究人員對腎細(xì)胞類型的多樣性存在分歧。為了找到人類腎臟細(xì)胞類型數(shù)量的答案，我們使用單細(xì)胞RNA測序?qū)Πl(fā)育中和成人腎臟組織進(jìn)行了研究，并將這些發(fā)現(xiàn)與單細(xì)胞RNA測序前時代的文獻(xiàn)進(jìn)行了比較。我們發(fā)現(xiàn)這些出版物展示了在整個發(fā)育過程中發(fā)現(xiàn)新細(xì)胞類型和中間細(xì)胞階段以及復(fù)雜的分子特征和譜系途徑的主要步驟。由于該技術(shù)的局限性，單細(xì)胞文獻(xiàn)中細(xì)胞類型的多樣性仍然存在差異。盡管如此，我們的分析接近了成年腎臟中 41 個已識別的腎臟譜系細(xì)胞群和 32 個非腎臟譜系的累積數(shù)量，此外當(dāng)然還有更多的發(fā)現(xiàn)。單細(xì)胞RNA測序研究中的各種定義和標(biāo)準(zhǔn)仍然需要達(dá)成共識，例如什么是細(xì)胞類型的定義。盡管如此，這項早期研究已經(jīng)證明對臨床和再生醫(yī)學(xué)具有重大影響，并顯示出增強(qiáng)復(fù)雜體外腎組織生成的潛力。
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英文題目：Single Cell and Plasma RNA Sequencing for RNA Liquid Biopsy for Hepatocellular Carcinoma
中文題目：用于肝細(xì)胞癌RNA液體活檢的單細(xì)胞和血漿RNA測序
發(fā)表時間：2021-08-31
發(fā)表雜志：Clin Chem
影響因子：8.327
DOI：10.1093/clinchem/hvab116
摘要：背景：人血漿含有由體內(nèi)多種細(xì)胞類型釋放的RNA轉(zhuǎn)錄物。單細(xì)胞轉(zhuǎn)錄組學(xué)分析允許以高分辨率闡明循環(huán)RNA分子的細(xì)胞來源，并已成功用于妊娠環(huán)境。我們探索了類似方法的應(yīng)用，以確定用于癌癥檢測的血漿RNA標(biāo)記。
方法：我們進(jìn)行單細(xì)胞RNA測序以破譯來自肝細(xì)胞癌 (HCC) 樣本的單細(xì)胞的轉(zhuǎn)錄組譜。我們鑒定了細(xì)胞類型特異性轉(zhuǎn)錄物，并用于推斷患有和未患有 HCC 的患者血漿 RNA 的細(xì)胞類型特異性基因特征 (CELSIG) 評分。
結(jié)果：基于4個HCC腫瘤組織及其配對的相鄰非腫瘤組織，鑒定出6個主要細(xì)胞群，包括肝細(xì)胞樣、膽管樣細(xì)胞、肌成纖維細(xì)胞、內(nèi)皮細(xì)胞、淋巴樣和髓樣細(xì)胞群。與非 HCC 參與者（n = 49）相比，HCC 患者（n = 14）術(shù)前血漿RNA樣本中肝細(xì)胞樣細(xì)胞的 CELSIG 評分顯著增加。在腫瘤切除術(shù)后3天內(nèi)，HCC 患者血漿RNA樣本中肝細(xì)胞樣細(xì)胞的CELSIG評分下降。與使用血漿中ALB轉(zhuǎn)錄物豐度 [曲線下面積 (AUC) 0.72)] 區(qū)分患有和不患有HCC的患者的能力相比，使用CELSIG評分觀察到了性能 (AUC：0.84) 的改進(jìn)。通過ddPCR分析進(jìn)一步驗證了血漿RNA中的肝細(xì)胞特異性轉(zhuǎn)錄標(biāo)記。肝細(xì)胞樣細(xì)胞和膽管細(xì)胞的CELSIG評分隨著患者的生存而變化。
結(jié)論：單細(xì)胞轉(zhuǎn)錄組學(xué)分析和血漿RNA測序的結(jié)合代表了一種開發(fā)新的非侵入性癌癥標(biāo)志物的方法。
IF＞9
Journal
Impact Factor
Title
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38.637
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30.822
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38.637
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30.822
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22.553
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20.507
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20.071
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20.479
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29.497
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26.602
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20.042
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27.603
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22.553
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20.711
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20.071
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Cell Stem Cell
20.860
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20.507
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20.582
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29.497
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Cancer Cell
26.602
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27.603
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27.000
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27.603
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21.567
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29.497
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29.497
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29.497
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20.479
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22.553
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20.582
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23.603
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17.373
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18.952
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13.493
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13.256
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14.415
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12.121
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14.588
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13.920
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14.612
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12.084
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13.440
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12.121
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Sci Immunol
13.440
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12.121
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Trends Biochem Sci
14.732
Single-Cell Proteomics
Sci Adv
13.116
Single-cell RNA-seq reveals a critical role of novel pro-inflammatory EndMT in mediating adverse remodeling in coronary artery-on-a-chip
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12.121
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Sci Adv
13.116
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14.251
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13.493
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12.121
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13.116
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12.121
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13.440
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11.093
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Biosens Bioelectron
10.257
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10.806
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Protein Cell
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10.419
CODEX multiplexed tissue imaging with DNA-conjugated antibodies
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10.806
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10.092
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10.092
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Biosens Bioelectron
10.257
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10.419
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10.419
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10.419
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10.419
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10.806
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10.419
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10.092
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Dev Cell
10.092
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10.502
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9.412
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9.727
Characterizing macrophage diversity in metastasis-bearing lungs reveals a lipid-associated macrophage subset
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9.727
Contacts with Macrophages Promote an Aggressive Nanomechanical Phenotype of Circulating Tumor Cells in Prostate Cancer
J Immunother Cancer
9.913
CXCR6 is required for antitumor efficacy of intratumoral CD8(+) T cell
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9.412
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Mol Neurodegener
9.599
Functional microRNA targetome undergoes degeneration-induced shift in the retina
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9.412
Microbiota-derived metabolites inhibit Salmonella virulent subpopulation development by acting on single-cell behaviors
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9.412
Morphogenesis and cell ordering in confined bacterial biofilms
Mol Aspects Med
9.577
NK cell and ILC heterogeneity in colorectal cancer. New perspectives from high dimensional data
Cancer Res
9.727
Oncostatin M Receptor-targeted antibodies suppress STAT3 signaling and inhibit ovarian cancer growth
J Immunother Cancer
9.913
PI3Kα inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8(+)T cells and promoting fatty acid metabolism
Curr Opin Chem Biol
9.689
Programmable tools for targeted analysis of epigenetic DNA modifications
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9.412
Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation
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9.412
Rapid interrogation of cancer cell of origin through CRISPR editing
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9.689
Recent advances in intravital microscopy for preclinical research
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9.412
Robust surface-to-mass coupling and turgor-dependent cell width determine bacterial dry-mass density
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9.412
SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression
Genes Dev
9.527
Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain
Redox Biol
9.986
Single-cell transcriptomics reveals lasting changes in the lung cellular landscape into adulthood after neonatal hyperoxic exposure
Plant Cell
9.618
Spatial and temporal localization of SPIRRIG and WAVE/SCAR reveal roles for these proteins in actin-mediated root hair development
Genes Dev
9.527
Transient genomic instability drives tumorigenesis through accelerated clonal evolution
編輯：張銀冰、植蓉丹、韓金、麥麗燕、陳小碟、陳泳茹、郭龍二、羅永健、陳俏芝、謝彩玲
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