Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming
Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC) reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715007925 |
| _version_ | 1828397669703221248 |
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| author | Swea-Ling Khaw Chua Min-Wen Cheng-Gee Koh Bing Lim Ng Shyh-Chang |
| author_facet | Swea-Ling Khaw Chua Min-Wen Cheng-Gee Koh Bing Lim Ng Shyh-Chang |
| author_sort | Swea-Ling Khaw |
| collection | DOAJ |
| description | Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC) reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis of pluripotency biomarkers further show that the Tcl1 oocyte factors improve the quality of reprogramming. Mechanistically, we find that the enhancement effect of Tcl1b1 depends on Akt, one of its putative targets. In contrast, Tcl1 suppresses the mitochondrial polynucleotide phosphorylase (PnPase) to promote reprogramming. Knockdown of PnPase rescues the inhibitory effect from Tcl1 knockdown during reprogramming, whereas PnPase overexpression abrogates the enhancement from Tcl1 overexpression. We further demonstrate that Tcl1 suppresses PnPase’s mitochondrial localization to inhibit mitochondrial biogenesis and oxidation phosphorylation, thus remodeling the metabolome. Hence, we identified the Tcl1-PnPase pathway as a critical mitochondrial switch during reprogramming. |
| first_indexed | 2024-12-10T08:51:39Z |
| format | Article |
| id | doaj.art-5218075313814fb4a989f1e631d6b1f9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T08:51:39Z |
| publishDate | 2015-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5218075313814fb4a989f1e631d6b1f92022-12-22T01:55:34ZengElsevierCell Reports2211-12472015-08-011271080108810.1016/j.celrep.2015.07.032Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance ReprogrammingSwea-Ling Khaw0Chua Min-Wen1Cheng-Gee Koh2Bing Lim3Ng Shyh-Chang4Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore 138672, SingaporeStem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore 138672, SingaporeSchool of Biological Sciences, Nanyang Technological University, Singapore 637551, SingaporeStem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore 138672, SingaporeStem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore 138672, SingaporeOocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC) reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis of pluripotency biomarkers further show that the Tcl1 oocyte factors improve the quality of reprogramming. Mechanistically, we find that the enhancement effect of Tcl1b1 depends on Akt, one of its putative targets. In contrast, Tcl1 suppresses the mitochondrial polynucleotide phosphorylase (PnPase) to promote reprogramming. Knockdown of PnPase rescues the inhibitory effect from Tcl1 knockdown during reprogramming, whereas PnPase overexpression abrogates the enhancement from Tcl1 overexpression. We further demonstrate that Tcl1 suppresses PnPase’s mitochondrial localization to inhibit mitochondrial biogenesis and oxidation phosphorylation, thus remodeling the metabolome. Hence, we identified the Tcl1-PnPase pathway as a critical mitochondrial switch during reprogramming.http://www.sciencedirect.com/science/article/pii/S2211124715007925 |
| spellingShingle | Swea-Ling Khaw Chua Min-Wen Cheng-Gee Koh Bing Lim Ng Shyh-Chang Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming Cell Reports |
| title | Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming |
| title_full | Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming |
| title_fullStr | Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming |
| title_full_unstemmed | Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming |
| title_short | Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming |
| title_sort | oocyte factors suppress mitochondrial polynucleotide phosphorylase to remodel the metabolome and enhance reprogramming |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715007925 |
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