دورية أكاديمية
Early enforcement of cell identity by a functional component of the terminally differentiated state.
| العنوان: | Early enforcement of cell identity by a functional component of the terminally differentiated state. |
|---|---|
| المؤلفون: | Zahra Bahrami-Nejad, Zhi-Bo Zhang, Stefan Tholen, Sanjeev Sharma, Atefeh Rabiee, Michael L Zhao, Fredric B Kraemer, Mary N Teruel |
| المصدر: | PLoS Biology, Vol 20, Iss 12, p e3001900 (2022) |
| بيانات النشر: | Public Library of Science (PLoS), 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | Biology (General), QH301-705.5 |
| الوصف: | How progenitor cells can attain a distinct differentiated cell identity is a challenging problem given the fluctuating signaling environment in which cells exist and that critical transcription factors are often not unique to a differentiation process. Here, we test the hypothesis that a unique differentiated cell identity can result from a core component of the differentiated state doubling up as a signaling protein that also drives differentiation. Using live single-cell imaging in the adipocyte differentiation system, we show that progenitor fat cells (preadipocytes) can only commit to terminally differentiate after up-regulating FABP4, a lipid buffer that is highly enriched in mature adipocytes. Upon induction of adipogenesis in mouse preadipocyte cells, we show that after a long delay, cells first abruptly start to engage a positive feedback between CEBPA and PPARG before then engaging, after a second delay, a positive feedback between FABP4 and PPARG. These sequential positive feedbacks both need to engage in order to drive PPARG levels past the threshold for irreversible differentiation. In the last step before commitment, PPARG transcriptionally increases FABP4 expression while fatty acid-loaded FABP4 increases PPARG activity. Together, our study suggests a control principle for robust cell identity whereby a core component of the differentiated state also promotes differentiation from its own progenitor state. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1544-9173 1545-7885 |
| Relation: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001900&type=printable; https://doaj.org/toc/1544-9173; https://doaj.org/toc/1545-7885 |
| DOI: | 10.1371/journal.pbio.3001900&type=printable |
| DOI: | 10.1371/journal.pbio.3001900 |
| URL الوصول: | https://doaj.org/article/5e8b430c32cf466e9f706c3fc859c631 |
| رقم الأكسشن: | edsdoj.5e8b430c32cf466e9f706c3fc859c631 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15449173 15457885 |
|---|---|
| DOI: | 10.1371/journal.pbio.3001900&type=printable |