Antler is the only organ that can fully regenerate annually in mammals. However, the regulatory pattern and mechanism of gene expression and cell differentiation during this process remain largely unknown. Here, we obtain comprehensive assembly and gene annotation of the sika deer (Cervus nippon) genome. Together with large-scale chromatin accessibility and gene expression data, we construct gene regulatory networks involved in antler regeneration, identifying four transcription factors, MYC, KLF4, NFE2L2, and JDP2 with high regulatory activity across whole regeneration process. Comparative studies and luciferase reporter assay suggest the MYC expression driven by a cervid-specific regulatory element might be important for antler regenerative ability. We further develop a model called cTOP which integrates single-cell data with bulk regulatory networks and find PRDM1, FOSL1, BACH1, and NFATC1 as potential pivotal factors in antler stem cell activation and osteogenic differentiation. Additionally, we uncover interactions within and between cell programs and pathways during the regeneration process. These findings provide insights into the gene and cell regulatory mechanisms of antler regeneration, particularly in stem cell activation and differentiation.

中文翻译：

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高质量的梅花鹿组学数据和综合分析揭示了鹿茸再生的基因和细胞调控


鹿角是哺乳动物唯一可以每年完全再生的器官。然而，在此过程中基因表达和细胞分化的调控模式和机制在很大程度上仍然未知。在这里，我们获得了梅花鹿 （Cervus nippon） 基因组的全面组装和基因注释。结合大规模染色质可及性和基因表达数据，我们构建了参与鹿茸再生的基因调控网络，鉴定了四个转录因子 MYC 、 KLF4 、 NFE2L2 和 JDP2 在整个再生过程中具有高调节活性。比较研究和荧光素酶报告基因测定表明，由鹿科动物特异性调节元件驱动的 MYC 表达可能对鹿茸再生能力很重要。我们进一步开发了一种称为 cTOP 的模型，该模型将单细胞数据与大量调控网络相结合，发现 PRDM1、FOSL1、BACH1 和 NFATC1 是鹿茸干细胞活化和成骨分化的潜在关键因素。此外，我们还揭示了再生过程中细胞程序和通路内部和之间的相互作用。这些发现为鹿茸再生的基因和细胞调控机制提供了见解，特别是在干细胞活化和分化方面。