Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells
Abstract Background The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. Methods Through a meta-analysis of previous genome-wide screening for...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-022-02976-z |
| _version_ | 1828787745922744320 |
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| author | Seong-Min Kim Eun-Ji Kwon Yun-Jeong Kim Young-Hyun Go Ji-Young Oh Seokwoo Park Jeong Tae Do Keun-Tae Kim Hyuk-Jin Cha |
| author_facet | Seong-Min Kim Eun-Ji Kwon Yun-Jeong Kim Young-Hyun Go Ji-Young Oh Seokwoo Park Jeong Tae Do Keun-Tae Kim Hyuk-Jin Cha |
| author_sort | Seong-Min Kim |
| collection | DOAJ |
| description | Abstract Background The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. Methods Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency. Results Loss of Shp2 increased naïve pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus iShp2 can replace the use of iMek1 for maintenance of naïve ESCs. Conclusions Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency. |
| first_indexed | 2024-12-12T00:38:27Z |
| format | Article |
| id | doaj.art-10f48ba44dd6404381ddc9d1687adfd5 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T00:38:27Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-10f48ba44dd6404381ddc9d1687adfd52022-12-22T00:44:18ZengBMCStem Cell Research & Therapy1757-65122022-07-0113111410.1186/s13287-022-02976-zDichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cellsSeong-Min Kim0Eun-Ji Kwon1Yun-Jeong Kim2Young-Hyun Go3Ji-Young Oh4Seokwoo Park5Jeong Tae Do6Keun-Tae Kim7Hyuk-Jin Cha8College of Pharmacy, Seoul National UniversityCollege of Pharmacy, Seoul National UniversityCollege of Pharmacy, Seoul National UniversityResearch Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy, Seoul National UniversityDepartment of Biomedical Sciences, Seoul National University College of MedicineDepartment of Stem Cell and Regenerative Biology, College of Animal Bioscience and Technology, Konkuk UniversityCollege of Pharmacy, Seoul National UniversityCollege of Pharmacy, Seoul National UniversityAbstract Background The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. Methods Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency. Results Loss of Shp2 increased naïve pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus iShp2 can replace the use of iMek1 for maintenance of naïve ESCs. Conclusions Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency.https://doi.org/10.1186/s13287-022-02976-zPtpn11Shp2Tyrosine phosphataseNaïve pluripotencySelf-renewalMek1 |
| spellingShingle | Seong-Min Kim Eun-Ji Kwon Yun-Jeong Kim Young-Hyun Go Ji-Young Oh Seokwoo Park Jeong Tae Do Keun-Tae Kim Hyuk-Jin Cha Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells Stem Cell Research & Therapy Ptpn11 Shp2 Tyrosine phosphatase Naïve pluripotency Self-renewal Mek1 |
| title | Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells |
| title_full | Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells |
| title_fullStr | Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells |
| title_full_unstemmed | Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells |
| title_short | Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells |
| title_sort | dichotomous role of shp2 for naive and primed pluripotency maintenance in embryonic stem cells |
| topic | Ptpn11 Shp2 Tyrosine phosphatase Naïve pluripotency Self-renewal Mek1 |
| url | https://doi.org/10.1186/s13287-022-02976-z |
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