Tracing the transitions from pluripotency to germ cell fate with CRISPR screening
| العنوان: | Tracing the transitions from pluripotency to germ cell fate with CRISPR screening |
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| المؤلفون: | Jamie A. Hackett, Ufuk Günesdogan, Yun Huang, M. Azim Surani, Kristjan A. Gretarsson, Toshihiro Kobayashi |
| المساهمون: | Surani, Azim [0000-0002-8640-4318], Hackett, Jamie [0000-0002-6237-3684], Apollo - University of Cambridge Repository |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Pluripotent Stem Cells, endocrine system, Somatic cell, Chromosomal Proteins, Non-Histone, Science, Population, Green Fluorescent Proteins, Gene regulatory network, General Physics and Astronomy, Embryonic Development, Receptors, Cytoplasmic and Nuclear, Mice, Transgenic, Cell fate determination, Biology, General Biochemistry, Genetics and Molecular Biology, Germline, 03 medical and health sciences, Mice, 0302 clinical medicine, Genes, Reporter, medicine, Basic Helix-Loop-Helix Transcription Factors, CRISPR, Animals, Clustered Regularly Interspaced Short Palindromic Repeats, education, lcsh:Science, 030304 developmental biology, 0303 health sciences, education.field_of_study, Multidisciplinary, Wnt signaling pathway, Gene Expression Regulation, Developmental, General Chemistry, Publisher Correction, 3. Good health, Cell biology, DNA-Binding Proteins, Repressor Proteins, Wnt Proteins, 030104 developmental biology, medicine.anatomical_structure, Epiblast, lcsh:Q, Positive Regulatory Domain I-Binding Factor 1, 030217 neurology & neurosurgery, Germ cell |
| الوصف: | Early mammalian development entails a series of cell fate transitions that includes transit through naïve pluripotency to post-implantation epiblast. This subsequently gives rise to primordial germ cells (PGC), the founding population of the germline lineage. To investigate the gene regulatory networks that control these critical cell fate decisions, we developed a compound-reporter system to track cellular identity in a model of PGC specification (PGC-like cells; PGCLC), and coupled it with unbiased genome-wide CRISPR screening. This enabled identification of key genes both for exit from pluripotency and for acquisition of PGC fate, with further characterisation revealing a central role for the transcription factors Nr5a2 and Zfp296 in germline ontogeny. Abrogation of these genes results in significantly impaired PGCLC development due to widespread activation (Nr5a2−/−) or inhibition (Zfp296−/−) of WNT pathway components. This leads to aberrant upregulation of the somatic programme or failure to appropriately activate germline genes in PGCLC, respectively, and consequently loss of germ cell identity. Overall our study places Zfp296 and Nr5a2 as key components of an expanded PGC gene regulatory network, and outlines a transferable strategy for identifying critical regulators of complex cell fate transitions. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6fb9889255e977595c6b5e92276e95a https://doaj.org/article/5c34654d52b24b38beedd6ab9c107982 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e6fb9889255e977595c6b5e92276e95a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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