| RRC ID |
67875
|
| 著者 |
Hayashi Y, Kuroda T, Kishimoto H, Wang C, Iwama A, Kimura K.
|
| タイトル |
Downregulation of rRNA transcription triggers cell differentiation.
|
| ジャーナル |
PLoS One
|
| Abstract |
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.
|
| 巻・号 |
9(5)
|
| ページ |
e98586
|
| 公開日 |
2014-1-1
|
| DOI |
10.1371/journal.pone.0098586
|
| PII |
PONE-D-13-54755
|
| PMID |
24879416
|
| PMC |
PMC4039485
|
| MeSH |
Animals
Cell Cycle / genetics
Cell Cycle Checkpoints / genetics
Cell Differentiation / genetics*
Cell Line
Cell Line, Tumor
Down-Regulation / genetics*
HL-60 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Myeloid Cells / metabolism
Pol1 Transcription Initiation Complex Proteins / genetics
RNA Polymerase I / genetics
RNA, Ribosomal / genetics*
RNA, Small Interfering / genetics
Transcription Factors
Transcription, Genetic / genetics*
|
| IF |
2.74
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535)
THP-1(RCB1189) |
