Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China.
Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China.
Cell Rep. 2023 Oct 31;42(10):113164. doi: 10.1016/j.celrep.2023.113164. Epub 2023 Sep 25.
Healthy Kupffer cell (KC) pool is dominated by embryonic KCs (EmKCs), preserving liver homeostasis. How the KC pool varies upon injury remains unclear. Using chimeric mice with bone marrow (BM) cells labeled with enhanced green fluorescent protein, we identify that BM monocyte-derived KCs (MoKCs) become dominant in cholestatic- or toxic-injured livers via immunofluorescence and mass cytometry. Single-cell RNA sequencing (scRNA-seq) unveils the enhanced proliferative, anti-apoptotic properties and repair potential of MoKCs compared with EmKCs, which are confirmed in vivo and ex vivo through flow cytometry, qPCR, Cell Counting Kit-8, and immunofluorescence. Furthermore, compared with EmKC-dominated livers, MoKC-dominated livers exhibit less functional damage, necrosis, and fibrosis under damage, as tested by serum alanine aminotransferase activity detection, H&E and Sirius red staining, qPCR, and western blot. Collectively, we highlight that MoKCs dominate the KC pool in injured livers and show enhanced proliferative and anti-apoptotic properties while also promoting repair and attenuating fibrosis.
健康的枯否细胞（KC）池主要由胚胎期 KC（EmKC）组成，维持着肝脏的内稳态。KC 池在损伤时如何变化尚不清楚。我们使用骨髓（BM）细胞用增强型绿色荧光蛋白标记的嵌合小鼠，通过免疫荧光和液质联用技术鉴定到，在胆汁淤积或毒性损伤的肝脏中，BM 单核细胞衍生的 KC（MoKC）通过免疫荧光和液质联用技术成为优势细胞。单细胞 RNA 测序（scRNA-seq）揭示了 MoKC 与 EmKC 相比，具有增强的增殖、抗凋亡特性和修复潜能，通过流式细胞术、qPCR、细胞计数试剂盒-8 和免疫荧光在体内和体外得到了证实。此外，与 EmKC 占主导的肝脏相比，MoKC 占主导的肝脏在损伤时表现出较少的功能损伤、坏死和纤维化，通过血清丙氨酸氨基转移酶活性检测、H&E 和天狼猩红染色、qPCR 和 Western blot 进行了测试。总之，我们强调 MoKC 在损伤的肝脏中占据 KC 池的主导地位，表现出增强的增殖和抗凋亡特性，同时促进修复并减轻纤维化。
