{"id":518,"date":"2020-09-18T08:44:28","date_gmt":"2020-09-18T11:44:28","guid":{"rendered":"http:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/?p=518"},"modified":"2020-12-02T18:04:36","modified_gmt":"2020-12-02T21:04:36","slug":"hypoxia-model","status":"publish","type":"post","link":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/hypoxia-model\/","title":{"rendered":"Hypoxia model"},"content":{"rendered":"\t\t
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Hypoxia-inducible factors (HIFs) are transcription factors that play an important role in the adaptive response to hypoxic conditions. HIFs are stabilized in hypoxia but degraded in normoxia. HIF-2\u03b1 subunit is involved in the regulation of transcription factors, controlling self-renewal of human pluripotent stem cells, embryonic development of the cardiovascular system and the regulation of angiogenesis by transcriptional activation of angiogenic cascades in physiological and pathological processes. Currently, modulation of HIF-2\u03b1 expression is considered to be a promising strategy for ischemic and cancer disease treatment. However, the problem of choosing the optimal methods of effective regulation of HIF-2\u03b1 still remains.<\/p>

We have obtained genetically modified human embryonic stem cells with increased expression of HIF-2\u03b1 under atmospheric oxygen conditions. The approach used is based on a CRISPR\/Cas9-mediated deletion within INT6<\/em> gene coding HIF-2\u03b1 inhibitor protein. A study of the resulting genetically modified human embryonic stem cells will contribute to an understanding of the connection between hypoxia and pluripotency. Obtaining endothelial derivatives of pluripotent stem cells with increased expression of HIF-2\u03b1 and enhanced regenerative potential may become the basis for the development of promising strategies for the treatment of ischemic diseases.<\/p>\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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The obtaining of CRISPR\/Cas 9-modified human pluripotent stem cell lines with upregulated hypoxia inducible factor HIF-2\u03b1 under atmospheric oxygen conditions. (A, B) The sequence of INT6 alleles with deleted regions in the genetically modified human ESCs (subclones H9, E12). (C) Immunocytochemical staining of pluripotent genetically modified human ESCs (subclones H9, E12). (D) Expression of INT6 mRNA, the INT6 protein and HIF-2\u03b1 mRNA in genetically modified human ESC (subclones H9, E12), ESCs in 5% O 2 (low O2) and ESCs cultured with hypoxia mimetic agents (DMOG, CoCl 2 ).<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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Hypoxia-inducible factors (HIFs) are transcription factors that play an important role in the adaptive response to hypoxic conditions. HIFs are stabilized in hypoxia but degraded in normoxia. HIF-2\u03b1 subunit is involved in the regulation of transcription factors, controlling self-renewal of human pluripotent stem cells, embryonic development of the cardiovascular system and the regulation of angiogenesis by transcriptional activation of angiogenic cascades in physiological and pathological processes. Currently, modulation of HIF-2\u03b1 expression is considered to be a promising strategy for ischemic and cancer disease treatment. However, the problem of choosing the optimal methods of effective regulation of HIF-2\u03b1 still remains.<\/p>

We have obtained genetically modified human embryonic stem cells with increased expression of HIF-2\u03b1 under atmospheric oxygen conditions. The approach used is based on a CRISPR\/Cas9-mediated deletion within INT6<\/em> gene coding HIF-2\u03b1 inhibitor protein. A study of the resulting genetically modified human embryonic stem cells will contribute to an understanding of the connection between hypoxia and pluripotency. Obtaining endothelial derivatives of pluripotent stem cells with increased expression of HIF-2\u03b1 and enhanced regenerative potential may become the basis for the development of promising strategies for the treatment of ischemic diseases.<\/p>\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Hypoxia-inducible factors (HIFs) are transcription factors that play an important role in the adaptive response to hypoxic conditions. HIFs are stabilized in hypoxia but degraded in normoxia. HIF-2\u03b1 subunit is involved in the regulation of transcription factors, controlling self-renewal of human pluripotent stem cells, embryonic development of the cardiovascular system and the regulation of angiogenesis […]<\/p>\n","protected":false},"author":31,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"elementor_header_footer","format":"standard","meta":[],"categories":[15],"tags":[53,54],"_links":{"self":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts\/518"}],"collection":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/users\/31"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/comments?post=518"}],"version-history":[{"count":19,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts\/518\/revisions"}],"predecessor-version":[{"id":1799,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts\/518\/revisions\/1799"}],"wp:attachment":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/media?parent=518"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/categories?post=518"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/tags?post=518"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}