Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming
Somatic cells can be directly reprogrammed into other cell lineages, which holds great promise for regenerative medicine. However, low efficiency and obscure mechanism hinder the application of direct reprogramming. Here, we show that overexpressing the hepatic-specific transcription factors (TFs) H...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2020-06, Vol.527 (3), p.723-729 |
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| creator | Wu, Huijiao Du, Cong Yang, Fan Zheng, Xiaofang Qiu, Dongbo Zhang, Qi Chen, Wenjie Xu, Yan |
| description | Somatic cells can be directly reprogrammed into other cell lineages, which holds great promise for regenerative medicine. However, low efficiency and obscure mechanism hinder the application of direct reprogramming. Here, we show that overexpressing the hepatic-specific transcription factors (TFs) HNF1α, FOXA3, and GATA4 was sufficient to convert human urinary epithelial cells (hUCs) into induced hepatocyte-like cells (iHeps). The obtained iHeps were confirmed to express various hepatocyte-specific genes with multiple mature hepatocyte functions. Moreover, autophagy-related genes P62, ULK1, BECN1, VPS34, and LC3B were upregulated in the early stage of reprogramming and knockout of P62 and BECN1 in hUCs with CRISPR/Cas9 technology increased the efficiency of direct reprogramming. Collectively, we established a non-invasive approach to convert hUCs into iHeps and provided a glimpse into the role of autophagy in this process.
•Human urinary epithelial cells were directly reprogrammed into induced hepatocytes.•Only three factors, HNF1α, FOXA3, and GATA4, were sufficient for reprogramming.•The induced cells had mature hepatocyte functions and morphology.•Suppressing autophagy-related genes enhanced the reprogramming efficiency. |
| doi_str_mv | 10.1016/j.bbrc.2020.03.119 |
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•Human urinary epithelial cells were directly reprogrammed into induced hepatocytes.•Only three factors, HNF1α, FOXA3, and GATA4, were sufficient for reprogramming.•The induced cells had mature hepatocyte functions and morphology.•Suppressing autophagy-related genes enhanced the reprogramming efficiency.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2020.03.119</identifier><identifier>PMID: 32439161</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Autophagy ; Cell Line ; Cells, Cultured ; Cellular Reprogramming ; Cellular Reprogramming Techniques ; CRISPR-Cas systems ; Direct reprogramming ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; epithelium ; GATA transcription factors ; Hepatocytes - cytology ; Hepatocytes - metabolism ; Human urinary epithelial cells ; Humans ; Induced hepatocyte-like cells ; medicine ; Urine - cytology</subject><ispartof>Biochemical and biophysical research communications, 2020-06, Vol.527 (3), p.723-729</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-9495cad0ed3138422a6995f4295288c55fdaa7f0064d0c4e0219f1ac7ac68cf13</citedby><cites>FETCH-LOGICAL-c389t-9495cad0ed3138422a6995f4295288c55fdaa7f0064d0c4e0219f1ac7ac68cf13</cites><orcidid>0000-0001-5778-1926</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X20306100$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32439161$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Huijiao</creatorcontrib><creatorcontrib>Du, Cong</creatorcontrib><creatorcontrib>Yang, Fan</creatorcontrib><creatorcontrib>Zheng, Xiaofang</creatorcontrib><creatorcontrib>Qiu, Dongbo</creatorcontrib><creatorcontrib>Zhang, Qi</creatorcontrib><creatorcontrib>Chen, Wenjie</creatorcontrib><creatorcontrib>Xu, Yan</creatorcontrib><title>Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Somatic cells can be directly reprogrammed into other cell lineages, which holds great promise for regenerative medicine. However, low efficiency and obscure mechanism hinder the application of direct reprogramming. Here, we show that overexpressing the hepatic-specific transcription factors (TFs) HNF1α, FOXA3, and GATA4 was sufficient to convert human urinary epithelial cells (hUCs) into induced hepatocyte-like cells (iHeps). The obtained iHeps were confirmed to express various hepatocyte-specific genes with multiple mature hepatocyte functions. Moreover, autophagy-related genes P62, ULK1, BECN1, VPS34, and LC3B were upregulated in the early stage of reprogramming and knockout of P62 and BECN1 in hUCs with CRISPR/Cas9 technology increased the efficiency of direct reprogramming. Collectively, we established a non-invasive approach to convert hUCs into iHeps and provided a glimpse into the role of autophagy in this process.
•Human urinary epithelial cells were directly reprogrammed into induced hepatocytes.•Only three factors, HNF1α, FOXA3, and GATA4, were sufficient for reprogramming.•The induced cells had mature hepatocyte functions and morphology.•Suppressing autophagy-related genes enhanced the reprogramming efficiency.</description><subject>Autophagy</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Cellular Reprogramming</subject><subject>Cellular Reprogramming Techniques</subject><subject>CRISPR-Cas systems</subject><subject>Direct reprogramming</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>epithelium</subject><subject>GATA transcription factors</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - metabolism</subject><subject>Human urinary epithelial cells</subject><subject>Humans</subject><subject>Induced hepatocyte-like cells</subject><subject>medicine</subject><subject>Urine - cytology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EokvLF-CAfOSSMP6TbCxxQRUUpEpcitSb5bXHu16SONgJ0h763XG0C0c4WRq99xvPe4S8YVAzYO37Y73bJVtz4FCDqBlTz8iGgYKKM5DPyQYA2oor9nhFXuV8BGBMtuoluRJcCsVatiFPdzhiMnOII42eHnAyc7SnGas-_EBqse8z9SkO9LAMZqRLCqNJJ4pTmA_YB9NfNGZ0tExoij2uJLPMcTqY_Ym61bOnLiS0M004pbhPZhjK8Ia88KbP-PryXpPvnz893H6p7r_dfb39eF9Z0am5UlI11jhAJ5joJOemVarxkquGd51tGu-M2fpyrXRgJQJnyjNjt8a2nfVMXJN3Z27Z_XPBPOsh5PXfZsS4ZM2bEogo6O3_pRJaAVLBSuVnqU0x54ReTykMJR3NQK8N6aNeG9JrQxqELg0V09sLf9kN6P5a_lRSBB_OAiyB_AqYdLYBR4vnALWL4V_834doo4c</recordid><startdate>20200630</startdate><enddate>20200630</enddate><creator>Wu, Huijiao</creator><creator>Du, Cong</creator><creator>Yang, Fan</creator><creator>Zheng, Xiaofang</creator><creator>Qiu, Dongbo</creator><creator>Zhang, Qi</creator><creator>Chen, Wenjie</creator><creator>Xu, Yan</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-5778-1926</orcidid></search><sort><creationdate>20200630</creationdate><title>Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming</title><author>Wu, Huijiao ; Du, Cong ; Yang, Fan ; Zheng, Xiaofang ; Qiu, Dongbo ; Zhang, Qi ; Chen, Wenjie ; Xu, Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-9495cad0ed3138422a6995f4295288c55fdaa7f0064d0c4e0219f1ac7ac68cf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Autophagy</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>Cellular Reprogramming</topic><topic>Cellular Reprogramming Techniques</topic><topic>CRISPR-Cas systems</topic><topic>Direct reprogramming</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>epithelium</topic><topic>GATA transcription factors</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - metabolism</topic><topic>Human urinary epithelial cells</topic><topic>Humans</topic><topic>Induced hepatocyte-like cells</topic><topic>medicine</topic><topic>Urine - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Huijiao</creatorcontrib><creatorcontrib>Du, Cong</creatorcontrib><creatorcontrib>Yang, Fan</creatorcontrib><creatorcontrib>Zheng, Xiaofang</creatorcontrib><creatorcontrib>Qiu, Dongbo</creatorcontrib><creatorcontrib>Zhang, Qi</creatorcontrib><creatorcontrib>Chen, Wenjie</creatorcontrib><creatorcontrib>Xu, Yan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Huijiao</au><au>Du, Cong</au><au>Yang, Fan</au><au>Zheng, Xiaofang</au><au>Qiu, Dongbo</au><au>Zhang, Qi</au><au>Chen, Wenjie</au><au>Xu, Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2020-06-30</date><risdate>2020</risdate><volume>527</volume><issue>3</issue><spage>723</spage><epage>729</epage><pages>723-729</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Somatic cells can be directly reprogrammed into other cell lineages, which holds great promise for regenerative medicine. However, low efficiency and obscure mechanism hinder the application of direct reprogramming. Here, we show that overexpressing the hepatic-specific transcription factors (TFs) HNF1α, FOXA3, and GATA4 was sufficient to convert human urinary epithelial cells (hUCs) into induced hepatocyte-like cells (iHeps). The obtained iHeps were confirmed to express various hepatocyte-specific genes with multiple mature hepatocyte functions. Moreover, autophagy-related genes P62, ULK1, BECN1, VPS34, and LC3B were upregulated in the early stage of reprogramming and knockout of P62 and BECN1 in hUCs with CRISPR/Cas9 technology increased the efficiency of direct reprogramming. Collectively, we established a non-invasive approach to convert hUCs into iHeps and provided a glimpse into the role of autophagy in this process.
•Human urinary epithelial cells were directly reprogrammed into induced hepatocytes.•Only three factors, HNF1α, FOXA3, and GATA4, were sufficient for reprogramming.•The induced cells had mature hepatocyte functions and morphology.•Suppressing autophagy-related genes enhanced the reprogramming efficiency.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32439161</pmid><doi>10.1016/j.bbrc.2020.03.119</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-5778-1926</orcidid></addata></record> |
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| subjects | Autophagy Cell Line Cells, Cultured Cellular Reprogramming Cellular Reprogramming Techniques CRISPR-Cas systems Direct reprogramming Epithelial Cells - cytology Epithelial Cells - metabolism epithelium GATA transcription factors Hepatocytes - cytology Hepatocytes - metabolism Human urinary epithelial cells Humans Induced hepatocyte-like cells medicine Urine - cytology |
| title | Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming |
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