دورية أكاديمية
SOX9 maintains human foetal lung tip progenitor state by enhancing WNT and RTK signalling.
| العنوان: | SOX9 maintains human foetal lung tip progenitor state by enhancing WNT and RTK signalling. |
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| المؤلفون: | Sun, Dawei, Llora Batlle, Oriol, van den Ameele, Jelle, Thomas, John C, He, Peng, Lim, Kyungtae, Tang, Walfred, Xu, Chufan, Meyer, Kerstin B, Teichmann, Sarah A, Marioni, John C, Jackson, Stephen P, Brand, Andrea H, Rawlins, Emma L |
| بيانات النشر: | EMBO Press Wellcome Trust/Cancer Research Uk Gurdon Institute EMBO J |
| سنة النشر: | 2022 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | CRISPRi screen, ETVs, Lung organoids, SOX9, Targeted DamID, Humans, Cell Differentiation, Lung, Signal Transduction, SOX9 Transcription Factor, Stem Cells |
| الوصف: | The balance between self-renewal and differentiation in human foetal lung epithelial progenitors controls the size and function of the adult organ. Moreover, progenitor cell gene regulation networks are employed by both regenerating and malignant lung cells, where modulators of their effects could potentially be of therapeutic value. Details of the molecular networks controlling human lung progenitor self-renewal remain unknown. We performed the first CRISPRi screen in primary human lung organoids to identify transcription factors controlling progenitor self-renewal. We show that SOX9 promotes proliferation of lung progenitors and inhibits precocious airway differentiation. Moreover, by identifying direct transcriptional targets using Targeted DamID, we place SOX9 at the centre of a transcriptional network, which amplifies WNT and RTK signalling to stabilise the progenitor cell state. In addition, the proof-of-principle CRISPRi screen and Targeted DamID tools establish a new workflow for using primary human organoids to elucidate detailed functional mechanisms underlying normal development and disease. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE189885Test; https://www.repository.cam.ac.uk/handle/1810/341074Test |
| DOI: | 10.17863/CAM.88501 |
| الإتاحة: | https://doi.org/10.17863/CAM.88501Test https://www.repository.cam.ac.uk/handle/1810/341074Test |
| حقوق: | All Rights Reserved ; http://www.rioxx.net/licenses/all-rights-reservedTest |
| رقم الانضمام: | edsbas.DE292A12 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.88501 |
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