Klf5 suppresses ERK signaling in mouse pluripotent stem cells.
Mouse embryonic stem cells (ESCs) are pluripotent stem cells, which have the ability to differentiate into all three germ layers: mesoderm, endoderm, and ectoderm. Proper levels of phosphorylated extracellular signal-regulated kinase (pERK) are critical for maintaining pluripotency, as elevated pERK...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6242311?pdf=render |
| _version_ | 1811221387511070720 |
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| author | Takuya Azami Ken Matsumoto Hyojung Jeon Tsuyoshi Waku Masafumi Muratani Hitoshi Niwa Satoru Takahashi Masatsugu Ema |
| author_facet | Takuya Azami Ken Matsumoto Hyojung Jeon Tsuyoshi Waku Masafumi Muratani Hitoshi Niwa Satoru Takahashi Masatsugu Ema |
| author_sort | Takuya Azami |
| collection | DOAJ |
| description | Mouse embryonic stem cells (ESCs) are pluripotent stem cells, which have the ability to differentiate into all three germ layers: mesoderm, endoderm, and ectoderm. Proper levels of phosphorylated extracellular signal-regulated kinase (pERK) are critical for maintaining pluripotency, as elevated pERK evoked by fibroblast growth factor (FGF) receptor activation results in differentiation of ESCs, while, conversely, reduction of pERK by a MEK inhibitor maintains a pluripotent ground state. However, mechanisms underlying proper control of pERK levels in mouse ESCs are not fully understood. Here, we find that Klf5, a Krüppel-like transcription factor family member, is a component of pERK regulation in mouse ESCs. We show that ERK signaling is overactivated in Klf5-KO ESCs and the overactivated ERK in Klf5-KO ESCs is suppressed by the introduction of Klf5, but not Klf2 or Klf4, indicating a unique role for Klf5 in ERK suppression. Moreover, Klf5 regulates Spred1, a negative regulator of the FGF-ERK pathway. Klf5 also facilitates reprogramming of EpiSCs into a naïve state in combination with a glycogen synthase kinase 3 inhibitor and LIF, and in place of a MEK inhibitor. Taken together, these results show for the first time that Klf5 has a unique role suppressing ERK activity in mouse ESCs. |
| first_indexed | 2024-04-12T07:58:24Z |
| format | Article |
| id | doaj.art-1072e5736745444582f84cea4374f0a8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T07:58:24Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1072e5736745444582f84cea4374f0a82022-12-22T03:41:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011311e020732110.1371/journal.pone.0207321Klf5 suppresses ERK signaling in mouse pluripotent stem cells.Takuya AzamiKen MatsumotoHyojung JeonTsuyoshi WakuMasafumi MurataniHitoshi NiwaSatoru TakahashiMasatsugu EmaMouse embryonic stem cells (ESCs) are pluripotent stem cells, which have the ability to differentiate into all three germ layers: mesoderm, endoderm, and ectoderm. Proper levels of phosphorylated extracellular signal-regulated kinase (pERK) are critical for maintaining pluripotency, as elevated pERK evoked by fibroblast growth factor (FGF) receptor activation results in differentiation of ESCs, while, conversely, reduction of pERK by a MEK inhibitor maintains a pluripotent ground state. However, mechanisms underlying proper control of pERK levels in mouse ESCs are not fully understood. Here, we find that Klf5, a Krüppel-like transcription factor family member, is a component of pERK regulation in mouse ESCs. We show that ERK signaling is overactivated in Klf5-KO ESCs and the overactivated ERK in Klf5-KO ESCs is suppressed by the introduction of Klf5, but not Klf2 or Klf4, indicating a unique role for Klf5 in ERK suppression. Moreover, Klf5 regulates Spred1, a negative regulator of the FGF-ERK pathway. Klf5 also facilitates reprogramming of EpiSCs into a naïve state in combination with a glycogen synthase kinase 3 inhibitor and LIF, and in place of a MEK inhibitor. Taken together, these results show for the first time that Klf5 has a unique role suppressing ERK activity in mouse ESCs.http://europepmc.org/articles/PMC6242311?pdf=render |
| spellingShingle | Takuya Azami Ken Matsumoto Hyojung Jeon Tsuyoshi Waku Masafumi Muratani Hitoshi Niwa Satoru Takahashi Masatsugu Ema Klf5 suppresses ERK signaling in mouse pluripotent stem cells. PLoS ONE |
| title | Klf5 suppresses ERK signaling in mouse pluripotent stem cells. |
| title_full | Klf5 suppresses ERK signaling in mouse pluripotent stem cells. |
| title_fullStr | Klf5 suppresses ERK signaling in mouse pluripotent stem cells. |
| title_full_unstemmed | Klf5 suppresses ERK signaling in mouse pluripotent stem cells. |
| title_short | Klf5 suppresses ERK signaling in mouse pluripotent stem cells. |
| title_sort | klf5 suppresses erk signaling in mouse pluripotent stem cells |
| url | http://europepmc.org/articles/PMC6242311?pdf=render |
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