Single-nucleus transcriptomic atlas of postnatal camel liver development identifies candidate adaptive features

Camels adapt to the harsh conditions by storing fat, which highlights the need to understand their liver adaptations. This study uses single-nucleus RNA sequencing to create a developmental atlas of the Bactrian camel (Camelus bactrianus) liver across newborn, weaning, and adult stages, analyzing 57,036 cells and identifying 19 cell types, including hepatocytes, liver sinusoidal endothelial cells (LSECs), and immune cells. We identified a special LSEC subtype, not seen in cattle or humans, with high hepatocyte growth factor activator (HGFAC) expression that activates hepatocyte growth factor (HGF). Hepatocyte pseudotime trajectories show a shift from proliferative to metabolically mature states, with fatty acid metabolism gene expression matching changes in milk composition. Immune cell composition shifts from Kupffer cell dominance in newborns to T cell dominance in adults, with high conservation between adult camels and cattle. These results reveal liver biochemical adaptations that support camel resilience to arid conditions, providing insights for human liver studies and livestock breeding in harsh agricultural settings.

骆驼通过储存脂肪以适应极端环境，这凸显了解析其肝脏适应性机制的必要性。本研究采用单细胞核RNA测序（single-nucleus RNA sequencing）技术，构建了双峰驼（Camelus bactrianus）新生、断奶及成年三个阶段的肝脏发育图谱，共分析57036个细胞，鉴定出19种细胞类型，包括肝细胞、肝血窦内皮细胞（liver sinusoidal endothelial cells，LSECs）以及免疫细胞。研究团队发现了一种未在牛或人类中被报道的特殊LSEC亚型，该亚型高表达肝细胞生长因子激活剂（hepatocyte growth factor activator，HGFAC），可激活肝细胞生长因子（hepatocyte growth factor，HGF）。肝细胞拟时轨迹显示，细胞从增殖状态向代谢成熟状态转变，其脂肪酸代谢基因的表达模式与乳汁成分的变化相匹配。免疫细胞组成从新生个体的库普弗细胞（Kupffer cell）主导，转变为成年个体的T细胞主导，且成年骆驼与牛的免疫细胞组成具有高度保守性。本研究揭示了支撑骆驼适应干旱环境的肝脏生化适应性机制，可为人类肝脏研究以及极端农业环境下的家畜育种提供新的研究视角。