RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
<p>Oxidative stress is known to induce melanocyte death, but the underlying mechanisms are incompletely understood. To identify oxidative stress-induced global gene expression changes in melanocytes, we treated PIG1 melanocytes with H<sub>2</sub>O<sub>2</sub> in a dose-...
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2019
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| _version_ | 1864513555861078016 |
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| author | Konduru Seetharama Sastry (14603308) |
| author2 | Haroon Naeem (209167) Younes Mokrab (6367) Aouatef Ismail Chouchane (14603311) |
| author2_role | author author author |
| author_facet | Konduru Seetharama Sastry (14603308) Haroon Naeem (209167) Younes Mokrab (6367) Aouatef Ismail Chouchane (14603311) |
| author_role | author |
| dc.creator.none.fl_str_mv | Konduru Seetharama Sastry (14603308) Haroon Naeem (209167) Younes Mokrab (6367) Aouatef Ismail Chouchane (14603311) |
| dc.date.none.fl_str_mv | 2019-12-04T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1155/2019/2841814 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/RNA-seq_Reveals_Dysregulation_of_Novel_Melanocyte_Genes_upon_Oxidative_Stress_Implications_in_Vitiligo_Pathogenesis/22082795 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Cell Biology Aging General Medicine Biochemistry |
| dc.title.none.fl_str_mv | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Oxidative stress is known to induce melanocyte death, but the underlying mechanisms are incompletely understood. To identify oxidative stress-induced global gene expression changes in melanocytes, we treated PIG1 melanocytes with H<sub>2</sub>O<sub>2</sub> in a dose- and time-dependent manner and performed RNA-seq. This approach allowed us to capture the events occurring early as well as late phase after treatment with H<sub>2</sub>O<sub>2</sub>. Our bioinformatics analysis identified differentially expressed genes involved in various biological processes of melanocytes which are known to contribute to the vitiligo development, such as apoptosis, autophagy, cell cycle regulation, cell adhesion, immune and inflammatory responses, melanocyte pluripotency, and developmental signaling such as WNT and NOTCH pathways. We uncovered several novel genes that are not previously described to be involved in melanocytic response to stress nor in vitiligo pathogenesis. Quantitative PCR and western blot analysis of selected proteins, performed on PIG1 and primary human epidermal melanocytes, confirmed the RNA-seq data. Interestingly, we discovered an aberrant regulation of several transcription factors that are involved in diabetes, neurological, and psychiatric diseases, all of which are comorbid conditions in patients with vitiligo. Our results may lead to a better understanding of the molecular mechanisms underlying vitiligo pathogenesis and help developing new drug targets for effective treatment. </p> <h2>Other information</h2> <p>Published in: Oxidative Medicine and Cellular Longevity<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1155/2019/2841814" target="_blank">http://dx.doi.org/10.1155/2019/2841814</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b693e63983a4634edca1b2c6bb40e58f |
| identifier_str_mv | 10.1155/2019/2841814 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22082795 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo PathogenesisKonduru Seetharama Sastry (14603308)Haroon Naeem (209167)Younes Mokrab (6367)Aouatef Ismail Chouchane (14603311)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesClinical sciencesCell BiologyAgingGeneral MedicineBiochemistry<p>Oxidative stress is known to induce melanocyte death, but the underlying mechanisms are incompletely understood. To identify oxidative stress-induced global gene expression changes in melanocytes, we treated PIG1 melanocytes with H<sub>2</sub>O<sub>2</sub> in a dose- and time-dependent manner and performed RNA-seq. This approach allowed us to capture the events occurring early as well as late phase after treatment with H<sub>2</sub>O<sub>2</sub>. Our bioinformatics analysis identified differentially expressed genes involved in various biological processes of melanocytes which are known to contribute to the vitiligo development, such as apoptosis, autophagy, cell cycle regulation, cell adhesion, immune and inflammatory responses, melanocyte pluripotency, and developmental signaling such as WNT and NOTCH pathways. We uncovered several novel genes that are not previously described to be involved in melanocytic response to stress nor in vitiligo pathogenesis. Quantitative PCR and western blot analysis of selected proteins, performed on PIG1 and primary human epidermal melanocytes, confirmed the RNA-seq data. Interestingly, we discovered an aberrant regulation of several transcription factors that are involved in diabetes, neurological, and psychiatric diseases, all of which are comorbid conditions in patients with vitiligo. Our results may lead to a better understanding of the molecular mechanisms underlying vitiligo pathogenesis and help developing new drug targets for effective treatment. </p> <h2>Other information</h2> <p>Published in: Oxidative Medicine and Cellular Longevity<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1155/2019/2841814" target="_blank">http://dx.doi.org/10.1155/2019/2841814</a></p>2019-12-04T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1155/2019/2841814https://figshare.com/articles/journal_contribution/RNA-seq_Reveals_Dysregulation_of_Novel_Melanocyte_Genes_upon_Oxidative_Stress_Implications_in_Vitiligo_Pathogenesis/22082795CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/220827952019-12-04T09:00:00Z |
| spellingShingle | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis Konduru Seetharama Sastry (14603308) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Cell Biology Aging General Medicine Biochemistry |
| status_str | publishedVersion |
| title | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| title_full | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| title_fullStr | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| title_full_unstemmed | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| title_short | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| title_sort | RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Cell Biology Aging General Medicine Biochemistry |