Downregulation of rRNA transcription triggers cell differentiation.
Downregulation of rRNA transcription triggers cell differentiation.
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DOI：
10.1371/journal.pone.0098586
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kimura K
中科院分区：
文献类型：
--
作者：
Hayashi Y;Kuroda T;Kishimoto H;Wang C;Iwama A;Kimura K
对各种刺激的反应对于维持体内平衡是必不可少的。核糖体RNA（rRNA）转录的下调是参与各种细胞过程（如细胞周期停滞和凋亡）对刺激的反应的机制之一。细胞分化是由细胞内和细胞外刺激引起的，并且与rRNA转录的下调以及细胞生长的减少有关。分化过程中rRNA转录的下调被认为有助于细胞生长的减少。然而，rRNA转录的下调可以诱导各种细胞过程;因此，它可以正向调节细胞分化。为了测试这种可能性，我们在HL-60和THP-1细胞中使用放线菌素D或PolI特异性转录因子IA（TIF-IA）的siRNA特异性下调rRNA转录，这两种细胞都具有分化潜力。rRNA转录的抑制诱导两种细胞系中的细胞分化，这通过共同分化标记物CD 11b的表达来证明。此外，在小鼠造血干细胞的离体培养物中TIF-IA敲低增加了骨髓细胞的百分比并降低了未成熟细胞的百分比。我们还评估了是否通过抑制细胞周期进程诱导分化，因为rRNA转录与细胞生长紧密相关。我们发现，细胞周期停滞而不影响rRNA转录并不诱导分化。据我们所知，我们的研究结果首次表明，rRNA水平的下调可能是诱导哺乳动物细胞分化的触发因素。此外，这种现象不仅仅是细胞周期停滞的反映。我们的研究结果提供了一个新的见解rRNA转录和细胞分化之间的关系。
Responding to various stimuli is indispensable for the maintenance of homeostasis. The downregulation of ribosomal RNA (rRNA) transcription is one of the mechanisms involved in the response to stimuli by various cellular processes, such as cell cycle arrest and apoptosis. Cell differentiation is caused by intra- and extracellular stimuli and is associated with the downregulation of rRNA transcription as well as reduced cell growth. The downregulation of rRNA transcription during differentiation is considered to contribute to reduced cell growth. However, the downregulation of rRNA transcription can induce various cellular processes; therefore, it may positively regulate cell differentiation. To test this possibility, we specifically downregulated rRNA transcription using actinomycin D or a siRNA for Pol I-specific transcription factor IA (TIF-IA) in HL-60 and THP-1 cells, both of which have differentiation potential. The inhibition of rRNA transcription induced cell differentiation in both cell lines, which was demonstrated by the expression of the common differentiation marker CD11b. Furthermore, TIF-IA knockdown in an ex vivo culture of mouse hematopoietic stem cells increased the percentage of myeloid cells and reduced the percentage of immature cells. We also evaluated whether differentiation was induced via the inhibition of cell cycle progression because rRNA transcription is tightly coupled to cell growth. We found that cell cycle arrest without affecting rRNA transcription did not induce differentiation. To the best of our knowledge, our results demonstrate the first time that the downregulation of rRNA levels could be a trigger for the induction of differentiation in mammalian cells. Furthermore, this phenomenon was not simply a reflection of cell cycle arrest. Our results provide a novel insight into the relationship between rRNA transcription and cell differentiation.
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影响因子：
12.4
作者：
通讯作者：
--
DOI：
10.1073/pnas.0800970105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Ali, Syed A.;Zaidi, Sayyed K.;Stein, Janet L.
通讯作者：
Stein, Janet L.
影响因子：
5.3
作者：
MARECHAL, V;ELENBAAS, B;LEVINE, AJ
通讯作者：
LEVINE, AJ
影响因子：
16
作者：
Boulon S;Westman BJ;Hutten S;Boisvert FM;Lamond AI
通讯作者：
Lamond AI
影响因子：
5.3
作者：
Dai, MS;Zeng, SX;Lu, H
通讯作者：
Lu, H