Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression.
Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression.
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DOI：
10.1371/journal.pone.0205883
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Klein DC
中科院分区：
文献类型：
--
作者：
Mays JC;Kelly MC;Coon SL;Holtzclaw L;Rath MF;Kelley MW;Klein DC
脊椎动物的松果体负责产生褪黑激素，这种激素在夜间会增加，从而影响昼夜节律和季节节律。这种增加与松果体转录组的巨大变化有关。在这里，通过对约 17,000 个松果体细胞的 mRNA 进行测序，对大鼠松果体转录组进行了单细胞分析，目的是对构成松果体的细胞进行分析，并检验松果体细胞因 Asmt 表达而区分的两个不同群体的提议，Asmt 编码将 N-乙酰血清素转化为褪黑激素的酶。此外，该分析还提供了基因表达的细胞特异性随时间变化的证据。鉴定出九种转录组不同的细胞类型：约 90% 被归类为产生褪黑激素的 α 和 β 松果体细胞（比例为 1:19）。非松果体细胞包括三种星形胶质细胞亚型、两种小胶质细胞亚型、血管和软脑膜细胞以及内皮细胞。 α-松果体细胞与 β-松果体细胞的 Asmt 转录物水平高出约 3 倍。此外，α-松果体细胞具有转录组差异，可能通过增加 Asmt 辅因子 S-腺苷甲硫氨酸的可用性来增强褪黑激素的形成，这是由于 S-腺苷甲硫氨酸前体 ATP 的产生增加所致。这些转录组差异包括产生 ATP 的氧化磷酸化转录组水平高出约 2 倍，核糖体转录组水平低约 8 倍，预计这将减少蛋白质合成对 ATP 的消耗。这些发现表明α-松果体细胞在松果体中具有特殊的作用：有效地O-甲基化β-松果体细胞产生和释放的N-乙酰血清素，从而提高褪黑激素合成的整体效率。我们还发现了七种细胞类型在夜间和白天发生的转录组变化，其中大部分发生在 β-松果体细胞中，较小程度地发生在 α-松果体细胞中；其中许多变化是通过异丙肾上腺素的肾上腺素刺激来模拟的。这项研究揭示的松果体细胞异质性为在单细胞分辨率下理解松果体细胞生物学提供了一个新的框架。
The vertebrate pineal gland is dedicated to the production of the hormone melatonin, which increases at night to influence circadian and seasonal rhythms. This increase is associated with dramatic changes in the pineal transcriptome. Here, single-cell analysis of the rat pineal transcriptome was approached by sequencing mRNA from ~17,000 individual pineal cells, with the goals of profiling the cells that comprise the pineal gland and examining the proposal that there are two distinct populations of pinealocytes differentiated by the expression of Asmt, which encodes the enzyme that converts N-acetylserotonin to melatonin. In addition, this analysis provides evidence of cell-specific time-of-day dependent changes in gene expression. Nine transcriptomically distinct cell types were identified: ~90% were classified as melatonin-producing α- and β-pinealocytes (1:19 ratio). Non-pinealocytes included three astrocyte subtypes, two microglia subtypes, vascular and leptomeningeal cells, and endothelial cells. α-Pinealocytes were distinguished from β-pinealocytes by ~3-fold higher levels of Asmt transcripts. In addition, α-pinealocytes have transcriptomic differences that likely enhance melatonin formation by increasing the availability of the Asmt cofactor S-adenosylmethionine, resulting from increased production of a precursor of S-adenosylmethionine, ATP. These transcriptomic differences include ~2-fold higher levels of the ATP-generating oxidative phosphorylation transcriptome and ~8-fold lower levels of the ribosome transcriptome, which is expected to reduce the consumption of ATP by protein synthesis. These findings suggest that α-pinealocytes have a specialized role in the pineal gland: efficiently O-methylating the N-acetylserotonin produced and released by β-pinealocytes, thereby improving the overall efficiency of melatonin synthesis. We have also identified transcriptomic changes that occur between night and day in seven cell types, the majority of which occur in β-pinealocytes and to a lesser degree in α-pinealocytes; many of these changes were mimicked by adrenergic stimulation with isoproterenol. The cellular heterogeneity of the pineal gland as revealed by this study provides a new framework for understanding pineal cell biology at single-cell resolution.
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影响因子：
3.5
作者：
Ivanov I;Kuhn H;Heydeck D
通讯作者：
Heydeck D
DOI：
10.1530/revreprod/3.1.13
发表时间：
1998-01-01
期刊：
REVIEWS OF REPRODUCTION
影响因子：
--
作者：
Arendt, J
通讯作者：
Arendt, J
影响因子：
6.2
作者：
Holtzclaw, LA;Pandhit, S;Russell, JT
通讯作者：
Russell, JT
影响因子：
4.1
作者：
ALOYO, VJ
通讯作者：
ALOYO, VJ
影响因子：
3.6
作者：
PEDERSEN, EB;FOX, LM;MCNULTY, JA
通讯作者：
MCNULTY, JA