Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm
Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-d...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-07-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115001526 |
| _version_ | 1818057968001744896 |
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| author | Avinash Waghray Néstor Saiz Anitha D. Jayaprakash Ana G. Freire Dmitri Papatsenko Carlos-Filipe Pereira Dung-Fang Lee Ran Brosh Betty Chang Henia Darr Julian Gingold Kevin Kelley Christoph Schaniel Anna-Katerina Hadjantonakis Ihor R. Lemischka |
| author_facet | Avinash Waghray Néstor Saiz Anitha D. Jayaprakash Ana G. Freire Dmitri Papatsenko Carlos-Filipe Pereira Dung-Fang Lee Ran Brosh Betty Chang Henia Darr Julian Gingold Kevin Kelley Christoph Schaniel Anna-Katerina Hadjantonakis Ihor R. Lemischka |
| author_sort | Avinash Waghray |
| collection | DOAJ |
| description | Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also, Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps to maintain a naive pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state toward mesoderm differentiation. |
| first_indexed | 2024-12-10T12:53:09Z |
| format | Article |
| id | doaj.art-14455f8caaf74166a117e2ebbcc23c4a |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-10T12:53:09Z |
| publishDate | 2015-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-14455f8caaf74166a117e2ebbcc23c4a2022-12-22T01:48:10ZengElsevierStem Cell Reports2213-67112015-07-01519711010.1016/j.stemcr.2015.05.009Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward MesodermAvinash Waghray0Néstor Saiz1Anitha D. Jayaprakash2Ana G. Freire3Dmitri Papatsenko4Carlos-Filipe Pereira5Dung-Fang Lee6Ran Brosh7Betty Chang8Henia Darr9Julian Gingold10Kevin Kelley11Christoph Schaniel12Anna-Katerina Hadjantonakis13Ihor R. Lemischka14Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10029, USAGraduate School, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADevelopmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10029, USADevelopmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USATbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also, Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps to maintain a naive pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state toward mesoderm differentiation.http://www.sciencedirect.com/science/article/pii/S2213671115001526 |
| spellingShingle | Avinash Waghray Néstor Saiz Anitha D. Jayaprakash Ana G. Freire Dmitri Papatsenko Carlos-Filipe Pereira Dung-Fang Lee Ran Brosh Betty Chang Henia Darr Julian Gingold Kevin Kelley Christoph Schaniel Anna-Katerina Hadjantonakis Ihor R. Lemischka Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm Stem Cell Reports |
| title | Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm |
| title_full | Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm |
| title_fullStr | Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm |
| title_full_unstemmed | Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm |
| title_short | Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm |
| title_sort | tbx3 controls dppa3 levels and exit from pluripotency toward mesoderm |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115001526 |
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