{"doi":"10.1016/j.scr.2020.101770","title":"Hypoxia/Hif1α prevents premature neuronal differentiation of neural stem cells through the activation of Hes1","abstract":null,"journal":"Stem Cell Research","year":2020,"id":622307,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1607822,"name":"Jiřina Procházková","orcid":null,"position":1,"is_corresponding":false},{"id":1607823,"name":"Veronika Šumberová","orcid":null,"position":2,"is_corresponding":false},{"id":1607824,"name":"Veronika Pánská","orcid":null,"position":3,"is_corresponding":false},{"id":656904,"name":"Hana Paculová","orcid":"0000-0002-4719-723X","position":4,"is_corresponding":false},{"id":1607825,"name":"Martina Kohutková Lánová","orcid":null,"position":5,"is_corresponding":false},{"id":1607826,"name":"Jan Mašek","orcid":null,"position":6,"is_corresponding":false},{"id":1607827,"name":"Dáša Bohačiaková","orcid":null,"position":7,"is_corresponding":false},{"id":1607829,"name":"Emma Rachel Andersson","orcid":null,"position":8,"is_corresponding":false},{"id":1607830,"name":"Jiří Pacherník","orcid":null,"position":9,"is_corresponding":false},{"id":1607821,"name":"Josef Večeřa","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hypoxia/Hif1α prevents premature neuronal differentiation of neural stem cells through the activation of Hes1","abstract":"Embryonic neural stem cells (NSCs), comprising neuroepithelial and radial glial cells, are indispensable precursors of neurons and glia in the mammalian developing brain. Since the process of neurogenesis occurs in a hypoxic environment, the question arises of how NSCs deal with low oxygen tension and whether it affects their stemness. Genes from the hypoxia-inducible factors (HIF) family are well known factors governing cellular response to hypoxic conditions. In this study, we have discovered that the endogenous stabilization of hypoxia-inducible factor 1α (Hif1α) during neural induction is critical for the normal development of the NSCs pool by preventing its premature depletion and differentiation. The knock-out of the Hif1α gene in mESC-derived neurospheres led to a decrease in self-renewal of NSCs, paralleled by an increase in neuronal differentiation. Similarly, neuroepithelial cells differentiated in hypoxia exhibited accelerated neurogenesis soon after Hif1α knock-down. In both models, the loss of Hif1α was accompanied by an immediate drop in neural repressor Hes1 levels while changes in Notch signaling were not observed. We found that active Hif1α/Arnt1 transcription complex bound to the evolutionarily conserved site in Hes1 gene promoter in both neuroepithelial cells and neural tissue of E8.5 - 9.5 embryos. Taken together, these results emphasize the novel role of Hif1α in the regulation of early NSCs population through the activation of neural repressor Hes1, independently of Notch signaling.","is_dataset_classified":null,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32276221","pmcid":null,"openalex_id":"https://openalex.org/W3013346247","authors":[],"funders":[{"funder_name":"Grantová Agentura České Republiky","grant_id":"15-13443Y","title":null},{"funder_name":"Grantová Agentura České Republiky","grant_id":"17-05466S","title":null},{"funder_name":"Ministerstvo Školství, Mládeže a Tělovýchovy","grant_id":"CZ.02.1.01/0.0/0.0/15_003/0000495","title":null},{"funder_name":"Åke Wiberg Foundation","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Państwowy Instytut Weterynaryjny - Państwowy Instytut Badawczy","grant_id":"","title":null},{"funder_name":"Åke Wiberg Stiftelse","grant_id":"","title":null},{"funder_name":"Central European Institute of Technology","grant_id":"","title":null},{"funder_name":"Neuron Nadační Fond Na Podporu Vědy","grant_id":"","title":null},{"funder_name":"Allen Foundation","grant_id":"","title":null},{"funder_name":"Karolinska Institutet","grant_id":"","title":null},{"funder_name":"Masarykova Univerzita","grant_id":"","title":null},{"funder_name":"Jeanssons Stiftelser","grant_id":"","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"","title":null}],"total_grants":13,"fwci":1.6404,"citation_percentile":0.83836771,"influential_citations":0,"citation_trend":[{"year":2020,"count":4},{"year":2021,"count":7},{"year":2022,"count":5},{"year":2023,"count":6},{"year":2024,"count":8},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.sciencedirect.com/science/article/pii/S187350612030074X/pdf","host_type":"journal"},{"url":"https://www.sciencedirect.com/science/article/pii/S187350612030074X/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S187350612030074X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S187350612030074X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.scr.2020.101770","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32276221","host_type":"repository"},{"url":"https://doaj.org/article/03ba4a2983a04dd9ab7c2dc8a299f4a1","host_type":"repository"},{"url":"https://dx.doi.org/10.1016/j.scr.2020.101770","host_type":""}],"fields_of_study":["Epigenetics and DNA Methylation","Cancer, Hypoxia, and Metabolism","Neurogenesis and neuroplasticity mechanisms","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Cell Differentiation","Cell Line","Hypoxia","Neural Stem Cells","Neurogenesis"],"mesh_terms":["Animals","Hypoxia","Cell Differentiation","Cell Line","Neurogenesis","Neural Stem Cells"],"keywords":["HES1","Biology","Neuroepithelial cell","Neural stem cell","Neurogenesis","Cell biology","Embryonic stem cell","Neurosphere","Notch signaling pathway","SOX2","Stem cell","Neural development","Neural tube","Transcription factor","Adult stem cell","Embryo","Signal transduction","Genetics","Gene","Hypoxia","Notch","neuroepithelium","Hif1α","QH301-705.5","Cell Differentiation","Cell Line","Neural Stem Cells","Animals","Biology (General)"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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