C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells
Summary: Sensorineural hearing loss is caused by the loss of sensory hair cells and neurons of the inner ear. Once lost, these cell types are not replaced. Two genes expressed in the developing inner ear are c-Myc and Sox2. We created immortalized multipotent otic progenitor (iMOP) cells, a fate-res...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114003518 |
| _version_ | 1811266277371543552 |
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| author | Kelvin Y. Kwan Jun Shen David P. Corey |
| author_facet | Kelvin Y. Kwan Jun Shen David P. Corey |
| author_sort | Kelvin Y. Kwan |
| collection | DOAJ |
| description | Summary: Sensorineural hearing loss is caused by the loss of sensory hair cells and neurons of the inner ear. Once lost, these cell types are not replaced. Two genes expressed in the developing inner ear are c-Myc and Sox2. We created immortalized multipotent otic progenitor (iMOP) cells, a fate-restricted cell type, by transient expression of C-MYC in SOX2-expressing otic progenitor cells. This activated the endogenous C-MYC and amplified existing SOX2-dependent transcripts to promote self-renewal. RNA-seq and ChIP-seq analyses revealed that C-MYC and SOX2 occupy over 85% of the same promoters. C-MYC and SOX2 target genes include cyclin-dependent kinases that regulate cell-cycle progression. iMOP cells continually divide but retain the ability to differentiate into functional hair cells and neurons. We propose that SOX2 and C-MYC regulate cell-cycle progression of these cells and that downregulation of C-MYC expression after growth factor withdrawal serves as a molecular switch for differentiation. : In this work, Kwan and colleagues generated an immortalized multipotent otic progenitor (iMOP) cell by transient expression of C-MYC in SOX2-expressing otic progenitor cells. The procedure activated endogenous C-MYC expression in the cells and amplified existing SOX2-dependent transcripts to promote self-renewal. Downregulation of C-MYC expression after growth factor withdrawal resulted in a molecular switch from self-renewal to otic differentiation. |
| first_indexed | 2024-04-12T20:39:13Z |
| format | Article |
| id | doaj.art-4f4b06fe09414c838206df140db9adc7 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-12T20:39:13Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-4f4b06fe09414c838206df140db9adc72022-12-22T03:17:28ZengElsevierStem Cell Reports2213-67112015-01-01414760C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor CellsKelvin Y. Kwan0Jun Shen1David P. Corey2Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Corresponding authorHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School Boston, MA 02115, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USAHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School Boston, MA 02115, USASummary: Sensorineural hearing loss is caused by the loss of sensory hair cells and neurons of the inner ear. Once lost, these cell types are not replaced. Two genes expressed in the developing inner ear are c-Myc and Sox2. We created immortalized multipotent otic progenitor (iMOP) cells, a fate-restricted cell type, by transient expression of C-MYC in SOX2-expressing otic progenitor cells. This activated the endogenous C-MYC and amplified existing SOX2-dependent transcripts to promote self-renewal. RNA-seq and ChIP-seq analyses revealed that C-MYC and SOX2 occupy over 85% of the same promoters. C-MYC and SOX2 target genes include cyclin-dependent kinases that regulate cell-cycle progression. iMOP cells continually divide but retain the ability to differentiate into functional hair cells and neurons. We propose that SOX2 and C-MYC regulate cell-cycle progression of these cells and that downregulation of C-MYC expression after growth factor withdrawal serves as a molecular switch for differentiation. : In this work, Kwan and colleagues generated an immortalized multipotent otic progenitor (iMOP) cell by transient expression of C-MYC in SOX2-expressing otic progenitor cells. The procedure activated endogenous C-MYC expression in the cells and amplified existing SOX2-dependent transcripts to promote self-renewal. Downregulation of C-MYC expression after growth factor withdrawal resulted in a molecular switch from self-renewal to otic differentiation.http://www.sciencedirect.com/science/article/pii/S2213671114003518 |
| spellingShingle | Kelvin Y. Kwan Jun Shen David P. Corey C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells Stem Cell Reports |
| title | C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells |
| title_full | C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells |
| title_fullStr | C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells |
| title_full_unstemmed | C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells |
| title_short | C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells |
| title_sort | c myc transcriptionally amplifies sox2 target genes to regulate self renewal in multipotent otic progenitor cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114003518 |
| work_keys_str_mv | AT kelvinykwan cmyctranscriptionallyamplifiessox2targetgenestoregulateselfrenewalinmultipotentoticprogenitorcells AT junshen cmyctranscriptionallyamplifiessox2targetgenestoregulateselfrenewalinmultipotentoticprogenitorcells AT davidpcorey cmyctranscriptionallyamplifiessox2targetgenestoregulateselfrenewalinmultipotentoticprogenitorcells |