Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity
Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity
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DOI：
10.1007/s13238-020-00705-x
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发表时间：
2020-03-19
期刊：
影响因子：
21.1
通讯作者：
Liebhaber, Stephen A.
中科院分区：
文献类型：
--
作者：
Ho, Yugong;Hu, Peng;Liebhaber, Stephen A.
在哺乳动物中，脑垂体腺驱动高度保守的生理过程。这些荷尔蒙控制的过程是躯体生长、青春期转化、生育、哺乳和新陈代谢的中心。目前的哺乳动物垂体前叶细胞模型主要建立在基于候选基因的免疫组织化学和mRNA分析基础上，表明垂体合成的七种激素中的每一种都是由特定的和排他性的细胞谱系产生的。然而，新出现的证据表明，激素特异性和细胞可塑性之间的关系更加复杂。在这里，我们应用大规模并行单细胞RNA测序(scRNA-seq)，结合基于互补成像的mRNAs和蛋白质的单细胞分析，在单细胞分辨率和主要生理需求的背景下，系统地定位成年雄性和雌性小鼠脑垂体的细胞类型多样性和功能状态异质性。这些定量的单细胞分析揭示了正常脑下垂体动态平衡下的性别特异性细胞类型组成，确定了与激素丰富的复杂补体相关的一系列细胞，并掩盖了产生间质和支持细胞类型的非激素。有趣的是，我们还鉴定了一个表达Pou1f1的细胞群体，其特征是具有独特的多激素基因表达谱。在对两种明确的生理胁迫的响应中，观察到主要激素产生细胞和推测的多激素细胞的细胞多样性和转录组图谱的动态变化。这些研究揭示了成年垂体细胞的复杂性和可塑性，并为进一步验证和扩大我们对垂体基因表达程序和激素产生的分子理解提供了丰富的资源。
The anterior pituitary gland drives highly conserved physiologic processes in mammalian species. These hormonally controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current cellular models of mammalian anteiror pituitary, largely built on candidate gene based immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests more complex relationship between hormone specificity and cell plasticity. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with complementary imaging-based single-cell analyses of mRNAs and proteins, to systematically map both cell-type diversity and functional state heterogeneity in adult male and female mouse pituitaries at single-cell resolution and in the context of major physiologic demands. These quantitative single-cell analyses reveal sex-specific cell-type composition under normal pituitary homeostasis, identify an array of cells associated with complex complements of hormone-enrichment, and undercover non-hormone producing interstitial and supporting cell-types. Interestingly, we also identified a Pou1f1-expressing cell population that is characterized by a unique multi-hormone gene expression profile. In response to two well-defined physiologic stresses, dynamic shifts in cellular diversity and transcriptome profiles were observed for major hormone producing and the putative multi-hormone cells. These studies reveal unanticipated cellular complexity and plasticity in adult pituitary, and provide a rich resource for further validating and expanding our molecular understanding of pituitary gene expression programs and hormone production.