Origination of the circadian clock system in stem cells regulates cell differentiation

Origination of the circadian clock system in stem cells regulates cell differentiation
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干细胞中生物钟系统的起源调节细胞分化

DOI:
10.1101/710590
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发表时间:
2019
期刊:
bioRxiv
影响因子:
--
通讯作者:
Endo Motomu
Endo Motomu
中科院分区:
--
文献类型:
--
作者:
Torii Kotaro;Inoue Keisuke;Bekki Keita;Haraguchi Kazuya;Kubo Minoru;Kondo Yuki;Suzuki Takamasa;Shimizu Hanako;Uemoto Kyohei;Saito Masato;Fukuda Hiroo;Araki Takashi;Endo Motomu

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生物钟调节各种生理反应。为了实现这一点,动物和植物在每个组织中都有不同的生物钟,这些生物钟针对该组织的各自功能进行了优化。然而,组织特异性生物钟是否以及如何参与细胞类型的特异性仍不清楚。在这里,通过使用新的分析管道实现单细胞转录组,我们以单细胞分辨率重建了细胞分化过程的实际时间序列,并发现生物钟通过转录因子BRI 1-EMS SUPPLYOR 1(BES 1)信号转导参与细胞分化过程。在这一通路中,BES 1对LHY表达的直接抑制触发了干细胞生物钟的重建。重建的生物钟通过微调表观遗传修饰、细胞命运决定和细胞周期的关键因素来调节细胞分化。因此,昼夜节律系统的建立先于细胞分化并指定细胞类型。
The circadian clock regulates various physiological responses. To achieve this, both animals and plants have distinct circadian clocks in each tissue that are optimized for that tissue’s respective functions. However, if and how the tissue-specific circadian clocks are involved in specification of cell types remains unclear. Here, by implementing a single-cell transcriptome with a new analytics pipeline, we have reconstructed an actual time-series of the cell differentiation process at single-cell resolution, and discovered that theArabidopsiscircadian clock is involved in the process of cell differentiation through transcription factor BRI1-EMS SUPPRESSOR 1 (BES1) signaling. In this pathway, direct repression ofLATE ELONGATED HYPOCOTYL(LHY) expression by BES1 triggers reconstruction of the circadian clock in stem cells. The reconstructed circadian clock regulates cell differentiation through fine-tuning of key factors for epigenetic modification, cell-fate determination, and the cell cycle. Thus, the establishment of circadian systems precedes cell differentiation and specifies cell types.
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