Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape.

Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape.
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DOI:
10.34133/research.0025
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发表时间:
2023
期刊:
Research (Washington, D.C.)
影响因子:
--
通讯作者:
Sun HZ
Sun HZ
中科院分区:
其他
文献类型:
--
作者:
Wu JJ;Zhu S;Tang YF;Gu F;Valencak TG;Liu JX;Sun HZ

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新生的反刍动物被认为是功能性的单胃动物。对新生反刍动物和成熟反刍动物之间的细胞差异缺乏了解,阻碍了家畜健康和生产性能的改善。在这里,我们对新生和成年牛的瘤胃、网状肌、皱胃、十二指肠、空肠、回肠、盲肠、结肠、直肠、肝脏、唾液腺和乳腺进行了单细胞RNA测序。破译了一份涵盖235,941个高质量单细胞和78种细胞类型的全面单细胞转录图谱。建立了牛细胞景观数据库(http://cattlecelllandscape.zju.edu.cn)),以精细地展示数据,并为广泛的研究社区提供牛细胞类型和亚型的有效注释。通过测量各组织类型上皮细胞的干性状态,我们发现新生前胃(瘤胃、网状组织和皱胃)上皮细胞与成年期相比在转录上更加模糊和随机,这与皱胃和肠道组织的转录模糊和随机性相反。犊牛早期前胃的快速发育是由具有高DNA修复活性和甲基化的上皮祖细胞推动的。此外,在新生小牛的前胃组织中,Megasphaera属通过DNA甲基化调节上皮祖细胞的转录可塑性。一种新的细胞类型,STOML3+细胞,被发现是新生儿特有的。显然,它在维持自身和肝脏微环境中的胆管细胞的干性方面起着至关重要的作用。我们的结果表明,依赖于年龄和微生物区系的细胞干可塑性驱动了反刍动物出生后的功能成熟。
Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants. Here, we performed the single-cell RNA sequencing on the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, rectum, liver, salivary gland, and mammary gland from newborn and adult cattle. A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered. A Cattle Cell Landscape database (http://cattlecelllandscape.zju.edu.cn) was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community. By measuring stemness states of epithelial cells in each tissue type, we revealed that the epithelial cells from newborn forestomach (rumen, reticulum, and omasum) were more transcriptionally indistinct and stochastic compared with the adult stage, which was in contrast to those of abomasum and intestinal tissues. The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation. Moreover, in the forestomach tissues of newborn calves, the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation. A novel cell type, the STOML3+ cell, was found to be newborn-specific. It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment. Our results reveal that the age- and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.
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