The rumen plays an essential role in the physiology and health of ruminants. The rumen undergoes substantial changes in size and function from birth to adulthood. The cellular and molecular mechanisms underlying these changes are not clear. This study was aimed to identify the transcription factors and signaling pathways mediating these changes in cattle. We found that the ratios of the emptied rumen, reticulum, omasum, and abomasum to body weight in adult steers were 4.8 (P < 0.01), 3.1 (P < 0.01), 6.0 (P < 0.01), and 0.8 (P = 0.9) times those in neonatal calves, respectively. The length of rumen papillae and the thickness of rumen epithelium, tunica mucosa and submucosa, tunica muscularis, and tunica serosa increased 7.4-, 2.0-, 3.0-, 2.9-, and 4.6-fold (P < 0.01 for all), respectively, from neonatal calves to adult steers. However, the density of rumen papillae was lower in adult steers than in neonatal calves (P < 0.05). The size of rumen epithelial cells was not different between neonatal calves and adult steers (P = 0.57). RNA sequencing identified 2,922 genes differentially expressed in the rumen between neonatal calves and adult steers. Functional enrichment analyses revealed that organ development, blood vessel development, Ras signaling, and Wnt signaling were among the functional terms enriched in genes downregulated in adult steers vs. neonatal calves and that fatty acid metabolism, immune responses, PPAR signaling, and Rap1 signaling were among those enriched in genes upregulated in adult steers vs. neonatal calves. Serum response factor (SRF), interferon regulatory factor 4, and purine-rich single-stranded DNA-binding protein alpha were among the major candidate transcription factors controlling the expression of genes upregulated, while TCF4, inhibitor of DNA binding 4, and snail family transcriptional repressor 2 were among those controlling the expression of genes downregulated in adult steers vs. neonatal calves. Taken together, these results suggest that the rumen grows by increasing the number, not the size, of cells from birth to adulthood, that the absorptive, metabolic, immune, and motility functions of the rumen are acquired or significantly enhanced during the postnatal life, and that the changes in rumen size and function from birth to adulthood are mediated by many candidate transcription factors, including SRF and TCF4, and many candidate signaling pathways, including the PPAR and Wnt signaling pathways.

中文翻译：

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鉴定介导牛出生后瘤胃生长和功能成熟的转录调节因子和信号通路


瘤胃在反刍动物的生理和健康中起着至关重要的作用。从出生到成年，瘤胃的大小和功能发生了重大变化。这些变化背后的细胞和分子机制尚不清楚。本研究旨在确定介导牛这些变化的转录因子和信号通路。我们发现成年阉牛排空瘤胃、网状、omasum 和 abomasum 与体重的比值分别为新生犊牛的 4.8 （P < 0.01） 、 3.1 （P < 0.01） 和 0.8 （P = 0.9） 倍。从新生犊牛到成年阉牛，瘤胃的长度和瘤胃上皮、粘膜粘膜和粘膜下层、肌肉膜和浆膜的厚度分别增加了 7.4 倍、 2.0 倍、 3.0 倍、 3.0 倍、 2.9 倍和 4.6 倍 （P < 0.01）。然而，成年阉牛瘤胃的密度低于新生犊牛 （P < 0.05）。新生犊牛和成年阉牛的瘤胃上皮细胞大小没有差异 （P = 0.57）。RNA 测序确定了 2,922 个基因在新生犊牛和成年阉牛的瘤胃中差异表达。功能富集分析显示，器官发育、血管发育、Ras 信号传导和 Wnt 信号传导是成年公牛与新生犊牛中下调基因中富集的功能项，而脂肪酸代谢、免疫反应、PPAR 信号传导和 Rap1 信号转导是成年公牛与新生犊牛中基因上调的基因中富集的基因之一。 血清反应因子 （SRF） 、干扰素调节因子 4 和富含嘌呤的单链 DNA 结合蛋白 α 是控制上调基因表达的主要候选转录因子，而 TCF4、DNA 结合抑制剂 4 和蜗牛家族转录抑制因子 2 是控制成年公牛与新生犊牛中下调基因表达的因子。综上所述，这些结果表明，从出生到成年，瘤胃是通过增加细胞的数量而不是大小来生长的，瘤胃的吸收、代谢、免疫和运动功能是在出生后获得或显着增强的，并且从出生到成年的瘤胃大小和功能的变化是由许多候选转录因子介导的， 包括 SRF 和 TCF4，以及许多候选信号转导通路，包括 PPAR 和 Wnt 信号转导通路。