Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle.
Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle.
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跨组织单细胞转录组景观揭示了关键细胞亚型及其在奶牛营养吸收和代谢中的潜在作用。
DOI：
10.1016/j.jare.2021.11.009
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发表时间：
2022-03
影响因子：
10.7
通讯作者：
Hui-Zeng Sun
中科院分区：
文献类型：
--
作者：
Jia-Jin Wu;Zhu, Senlin;Gu, Fengfei;Valencak, Teresa G.;Jian-Xin Liu;Hui-Zeng Sun
关键词：
首次在牛单细胞图谱中发现55种细胞类型及其特异性标记；前胃3种上皮祖细胞样细胞亚型的鉴定与验证揭示中性粒细胞在乳腺中的重要但非免疫功能；揭示具有优先营养摄取的关键细胞亚型；发现Th17细胞调节前胃上皮细胞对营养物质转运的反应。奶牛是满足全球对高质量动物蛋白生产需求的一种至关重要的反刍动物。将人体不易消化的生物质转化为高度可消化和营养丰富的牛奶的复杂生物过程是由各种组织精心策划的。然而，对关键代谢组织的细胞组成和功能了解不足，阻碍了国内反刍动物健康和生产性能的改善。本研究在单细胞分辨率下研究了泌乳奶牛的细胞异质性、代谢特征和相互作用。对泌乳奶牛的瘤胃、网状、瓣胃、皱胃、回肠、直肠、肝脏、唾液腺、乳腺和外周血进行了无偏倚的单细胞rna测序和分析。免疫荧光和荧光原位杂交验证细胞的身份。在这项研究中，我们构建了一个包含88,013个优质单细胞（500个<基因< 4,000个，UMI < 50,000个，线粒体基因比例< 40%或15%）的单细胞景观，并鉴定了55种主要的哺乳奶牛细胞类型。我们对与营养转运相关的上皮细胞的基因表达谱和代谢特征进行了系统的调查，揭示了细胞亚型对不同营养物质有优先吸收。重要的是，我们发现T辅助型17 （Th17）细胞（高表达CD4和IL17A）在前胃组织中特异性富集，并主要通过IL-17信号传导与具有高潜在短链脂肪酸摄取能力的上皮细胞亚型相互作用。此外，il17rahighil17rhigh细胞（IL17RA和IL17RC表达水平均大于0.25的上皮细胞）与其他细胞的比较解释了Th17细胞在调节上皮细胞对前胃营养转运的转录反应中的重要性。这一发现增强了我们对反刍动物细胞生物学的理解，并为提高奶牛的动物产量开辟了新的途径。
Discover 55 cell types and their specific markers in the first single-cell atlas of cattle; Identify and verify 3 epithelial progenitor-like cell subtypes in the forestomach Reveal vital but nonimmune functions of neutrophils in the mammary gland; Uncover key cell subtypes with preferential nutrient uptake; Find Th17 cells regulate epithelial cells responding to nutrient transport in the forestomach. Dairy cattle are a vitally important ruminant in meeting the demands for high-quality animal protein production worldwide. The complicated biological process of converting human indigestible biomass into highly digestible and nutritious milk is orchestrated by various tissues. However, poorly understanding of the cellular composition and function of the key metabolic tissues hinders the improvement of health and performance of domestic ruminants. The cellular heterogeneity, metabolic features, interactions across ten tissue types of lactating dairy cattle were studied at single-cell resolution in the current study. Unbiased single-cell RNA-sequencing and analysis were performed on the rumen, reticulum, omasum, abomasum, ileum, rectum, liver, salivary gland, mammary gland, and peripheral blood of lactating dairy cattle. Immunofluorescences and fluorescence in situ hybridization were performed to verify cell identity. In this study, we constructed a single-cell landscape covering 88,013 high-quality (500 < genes < 4,000, UMI < 50, 000, and mitochondrial gene ratio < 40% or 15%) single cells and identified 55 major cell types in lactating dairy cattle. Our systematic survey of the gene expression profiles and metabolic features of epithelial cells related to nutrient transport revealed cell subtypes that have preferential absorption of different nutrients. Importantly, we found that T helper type 17 (Th17) cells (highly expressing CD4 and IL17A) were specifically enriched in the forestomach tissues and predominantly interacted with the epithelial cell subtypes with high potential uptake capacities of short-chain fatty acids through IL-17 signaling. Furthermore, the comparison between IL17RAhighIL17RChigh cells (epithelial cells with IL17RA and IL17RC expression levels both greater than 0.25) and other cells explained the importance of Th17 cells in regulating the epithelial cellular transcriptional response to nutrient transport in the forestomach. The findings enhance our understanding of the cellular biology of ruminants and open new avenues for improved animal production of dairy cattle.
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