小柯机器人

近日，比利时根特大学Charlotte L. Scott、Martin Guilliams等研究人员合作揭示不同的和进化上保守的肝巨噬细胞微环境。相关论文于2022年1月11日在线发表在《细胞》杂志上。

研究人员报道了健康和肥胖的人类以及小鼠肝脏的空间蛋白质组图谱，并结合了单细胞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，研究人员提供了经过验证的策略来可靠地区分和定位所有肝细胞，包括胆管中的脂质相关巨噬细胞（LAM）群。然后，研究人员将这个图谱在七个物种中比对，从而揭示出真正的库普弗细胞和LAM的保守程序。

研究人员还揭示了这些巨噬细胞各自的空间分辨细胞微环境和驱动其独特转录组特性的微环境回路。研究人员证明LAM是由局部脂质暴露诱导的，导致它们在小鼠和人类肝脏的脂肪变性区域中被诱导，而库普弗细胞的发育关键取决于它们通过进化上保守的ALK1-BMP9/10轴与肝星状细胞的相互作用。

据了解，肝脏是人体最大的实体器官，但其特征仍然不完整。

附：英文原文

Title: Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

Author: Martin Guilliams, Johnny Bonnardel, Birthe Haest, Bart Vanderborght, Camille Wagner, Anneleen Remmerie, Anna Bujko, Liesbet Martens, Tinne Thoné, Robin Browaeys, Federico F. De Ponti, Bavo Vanneste, Christian Zwicker, Freya R. Svedberg, Tineke Vanhalewyn, Amanda Gonalves, Saskia Lippens, Bert Devriendt, Eric Cox, Giuliano Ferrero, Valerie Wittamer, Andy Willaert, Suzanne J.F. Kaptein, Johan Neyts, Kai Dallmeier, Peter Geldhof, Stijn Casaert, Bart Deplancke, Peter ten Dijke, Anne Hoorens, Aude Vanlander, Frederik Berrevoet, Yves Van Nieuwenhove, Yvan Saeys, Wouter Saelens, Hans Van Vlierberghe, Lindsey Devisscher, Charlotte L. Scott

Issue&Volume: 2022-01-11

Abstract: 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.

DOI: 10.1016/j.cell.2021.12.018

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01481-1