Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.
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空间蛋白质基因组学揭示了独特且在进化上保守的肝脏巨噬细胞生态位。
DOI：
10.1016/j.cell.2021.12.018
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发表时间：
2022-01-20
期刊：
影响因子：
64.5
通讯作者：
Scott CL
中科院分区：
文献类型：
--
作者：
Guilliams M;Bonnardel J;Haest B;Vanderborght B;Wagner C;Remmerie A;Bujko A;Martens L;Thoné T;Browaeys R;De Ponti FF;Vanneste B;Zwicker C;Svedberg FR;Vanhalewyn T;Gonçalves A;Lippens S;Devriendt B;Cox E;Ferrero G;Wittamer V;Willaert A;Kaptein SJF;Neyts J;Dallmeier K;Geldhof P;Casaert S;Deplancke B;Ten Dijke P;Hoorens A;Vanlander A;Berrevoet F;Van Nieuwenhove Y;Saeys Y;Saelens W;Van Vlierberghe H;Devisscher L;Scott CL
肝脏是人体内最大的实体器官，但其特征仍不完全。在这里，我们提出了一个空间蛋白基因组图谱的健康和肥胖的人类和小鼠肝脏结合单细胞CITE-seq，单核测序，空间转录组学和空间蛋白质组学。通过整合这些多组学数据集，我们提供了有效的策略来可靠地区分和定位所有肝细胞，包括胆管处的脂质相关巨噬细胞（LAM）群体。然后，我们在7个物种中比对该图谱，揭示了真正的枯否细胞和LAMs的保守程序。我们还揭示了这些巨噬细胞各自的空间分辨细胞龛和驱动其独特的转录组身份的微环境电路。我们证明了LAMs是由局部脂质暴露诱导的，导致它们在小鼠和人肝脏的脂肪变性区域中的诱导，而枯否细胞的发育关键取决于它们通过进化上保守的ALK 1-BMP 9/10轴与肝星状细胞的串扰。健康和肥胖小鼠和人类肝脏的空间蛋白基因组单细胞图谱所有肝细胞的经验证的流式细胞术和显微镜检查组LAM在瘦和肥胖肝脏中的位置不同进化保守的BMP 9/10-ALK 1轴对KC发育至关重要通过将单细胞和核测序与RNA和蛋白质的空间定位相结合，健康和肥胖人类和小鼠肝脏的这一巨大的空间蛋白基因组图谱提供了鉴定和定位所有肝细胞的方法，并提供了对肝髓样细胞的了解，包括鉴定用于分离和定位肝巨噬细胞的可靠表面标志物，健康和脂肪变性肝脏中脂质相关巨噬细胞的表征，库普弗细胞发育的关键调控轴的确定，以及跨7个物种（包括鸡和斑马鱼）库普弗细胞的保守核心基因表达特征的鉴定。
The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis. Spatial proteogenomic single-cell atlas of healthy and obese murine and human liver Validated flow cytometry and microscopy panels for all hepatic cells LAMs are differentially located in the lean and obese liver Evolutionary conserved BMP9/10-ALK1 axis is essential for KC development By combining single-cell and -nucleus sequencing with spatial mapping of RNA and proteins, this vast spatial proteogenomic atlas of healthy and obese human and mouse livers presents methods to identify and localize all hepatic cells and provides insights into hepatic myeloid cells, including identification of reliable surface markers for isolation and localization of hepatic macrophages, characterization of lipid-associated macrophages in both healthy and steatotic livers, determination of a key regulatory axis of Kupffer cell development, and identification of a conserved core gene expression signature of Kupffer cells across 7 species, including chickens and zebrafish.
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影响因子：
64.8
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
通讯作者：
Itzkovitz S
影响因子：
32.4
作者：
De Simone G;Andreata F;Bleriot C;Fumagalli V;Laura C;Garcia-Manteiga JM;Di Lucia P;Gilotto S;Ficht X;De Ponti FF;Bono EB;Giustini L;Ambrosi G;Mainetti M;Zordan P;Bénéchet AP;Ravà M;Chakarov S;Moalli F;Bajenoff M;Guidotti LG;Ginhoux F;Iannacone M
通讯作者：
Iannacone M
影响因子：
14.9
作者：
Gans JD;Wolinsky M
通讯作者：
Wolinsky M
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
16
作者：
Goumans, MJ;Valdimarsdottir, G;ten Dijke, P
通讯作者：
ten Dijke, P