دورية أكاديمية
Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation
| العنوان: | Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation |
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| المؤلفون: | Anneliis Ihermann-Hella, Tsuyoshi Hirashima, Jussi Kupari, Kristen Kurtzeborn, Hao Li, Hyuk Nam Kwon, Cristina Cebrian, Abdul Soofi, Arvydas Dapkunas, Ilkka Miinalainen, Gregory R. Dressler, Michiyuki Matsuda, Satu Kuure |
| المصدر: | Stem Cell Reports, Vol 11, Iss 4, Pp 912-928 (2018) |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
| مصطلحات موضوعية: | Medicine (General), R5-920, Biology (General), QH301-705.5 |
| الوصف: | Summary: The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Förster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche. Molecularly, MAPK/ERK activity regulates niche organization and communication with extracellular matrix through PAX2 and ITGA8, and is needed for CITED1 expression denoting undifferentiated status. MAPK/ERK activation in nephron precursors propels differentiation by priming cells for distal and proximal fates induced by the Wnt and Notch pathways. Thus, our results demonstrate a mechanism through which MAPK/ERK activity controls both progenitor maintenance and differentiation by regulating a distinct set of targets, which maintain the biomechanical milieu of tissue-residing progenitors and prime precursors for nephrogenesis. : In this article, Ihermann-Hella and colleagues show that MAPK/ERK activity, typically altered in several cancers, plays a dual function in regulation of embryonic nephron progenitors. MAPK/ERK activity maintains nephron progenitors within their in vivo niche by regulating PAX2 and ITGA8, and fosters nephrogenesis in early differentiating nephrons. Utilization of these findings may substantially improve prospective iPSC-derived kidney organoid differentiation. Keywords: progenitor cells, nephron progenitor, self-renewal, differentiation, stem cell niche, intracellular signaling, signaling strength, MAPK/ERK activity, kidney development, nephrogenesis |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2213-6711 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2213671118303564; https://doaj.org/toc/2213-6711 |
| DOI: | 10.1016/j.stemcr.2018.08.012 |
| URL الوصول: | https://doaj.org/article/10e4f35dd807468285ed6280c1c407db |
| رقم الأكسشن: | edsdoj.10e4f35dd807468285ed6280c1c407db |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22136711 |
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| DOI: | 10.1016/j.stemcr.2018.08.012 |