An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs
Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biologi...
Gespeichert in:
| Veröffentlicht in: | Cell death and differentiation 2012-06, Vol.19 (6), p.937-946 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 946 |
|---|---|
| container_issue | 6 |
| container_start_page | 937 |
| container_title | Cell death and differentiation |
| container_volume | 19 |
| creator | Garibaldi, F Cicchini, C Conigliaro, A Santangelo, L Cozzolino, A M Grassi, G Marchetti, A Tripodi, M Amicone, L |
| description | Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene
HNF4α
, directly represses the expression of the epithelial microRNAs
(miRs)-200c
and -
34a
, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4
α
, previously identified as a transcriptional repressor of
Snail
, induces the
miRs-34a
and -
200a, b, c
that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4
α
and miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation. |
| doi_str_mv | 10.1038/cdd.2011.175 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3354047</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1011536823</sourcerecordid><originalsourceid>FETCH-LOGICAL-c460t-a7b275b3d86c9f035b6fda4df43e3b341e03a1c93135dbd82ea085ab49b0b9b73</originalsourceid><addsrcrecordid>eNptkstu1DAUhiMEoqWwY428ZEEGO3ZuG6RRRRmkUZG4rC3bOZmcKrGD7Qz0sXgBHoFnwtMp5SIkS7Z0Pv_H5_efZU8ZXTHKm5em61YFZWzF6vJedspEXeWloPx-OvOS5i0V9Un2KIQrSmlVt9XD7KQoGG8Zp6fZ97UlMGOIKqIhE1rMDXqzYPTXREP8AmBJHIBEr2wwHueIzpJemeh8IB-swpEo25HN5YX48Y0YZ6N3YyAj7sGTEGEiBsYjM8CsojPXEUgPKi4eAoGvg_MR7Y64eXYBU83DbhnVTZ-0DhIWQsjRDqjxBp3QePf-ch0eZw96NQZ4crufZZ8uXn883-Tbd2_enq-3uREVjbmqdVGXmndNZdqe8lJXfadE1wsOXHPBgHLFTMuTY53umgIUbUqlRaupbnXNz7JXR9150RN0BtKUapSzx0n5a-kUyr8rFge5c3vJefoLcRDIjwLDP9c2662cVRpy8ZLStqFMiD1L_PPbht59XiBEOWE4GKksuCVIln685FVT8IS-OKLJkxA89Hf6jMpDRGSKiDxERKaIJPzZn6Pcwb8y8fupIZXsDry8cou3yd7_C_4Ex23NjQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1011536823</pqid></control><display><type>article</type><title>An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Garibaldi, F ; Cicchini, C ; Conigliaro, A ; Santangelo, L ; Cozzolino, A M ; Grassi, G ; Marchetti, A ; Tripodi, M ; Amicone, L</creator><creatorcontrib>Garibaldi, F ; Cicchini, C ; Conigliaro, A ; Santangelo, L ; Cozzolino, A M ; Grassi, G ; Marchetti, A ; Tripodi, M ; Amicone, L</creatorcontrib><description>Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene
HNF4α
, directly represses the expression of the epithelial microRNAs
(miRs)-200c
and -
34a
, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4
α
, previously identified as a transcriptional repressor of
Snail
, induces the
miRs-34a
and -
200a, b, c
that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4
α
and miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/cdd.2011.175</identifier><identifier>PMID: 22139130</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apoptosis ; Biochemistry ; Biochemistry, Molecular Biology ; Biomedical and Life Sciences ; Cell Biology ; Cell Cycle Analysis ; Cell Differentiation ; Cellular Biology ; Epithelial-Mesenchymal Transition ; Hepatocyte Nuclear Factor 4 ; Hepatocyte Nuclear Factor 4 - deficiency ; Hepatocyte Nuclear Factor 4 - genetics ; Hepatocyte Nuclear Factor 4 - metabolism ; Hepatocytes ; Hepatocytes - metabolism ; Life Sciences ; Liver ; Liver - cytology ; Liver - metabolism ; Mice ; Mice, Knockout ; MicroRNAs ; MicroRNAs - metabolism ; Original Paper ; Snail Family Transcription Factors ; Stem Cells ; Stem Cells - metabolism ; Transcription Factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription, Genetic</subject><ispartof>Cell death and differentiation, 2012-06, Vol.19 (6), p.937-946</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2012 Macmillan Publishers Limited 2012 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-a7b275b3d86c9f035b6fda4df43e3b341e03a1c93135dbd82ea085ab49b0b9b73</citedby><cites>FETCH-LOGICAL-c460t-a7b275b3d86c9f035b6fda4df43e3b341e03a1c93135dbd82ea085ab49b0b9b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354047/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354047/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,41467,42536,51298,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22139130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://riip.hal.science/pasteur-00980144$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Garibaldi, F</creatorcontrib><creatorcontrib>Cicchini, C</creatorcontrib><creatorcontrib>Conigliaro, A</creatorcontrib><creatorcontrib>Santangelo, L</creatorcontrib><creatorcontrib>Cozzolino, A M</creatorcontrib><creatorcontrib>Grassi, G</creatorcontrib><creatorcontrib>Marchetti, A</creatorcontrib><creatorcontrib>Tripodi, M</creatorcontrib><creatorcontrib>Amicone, L</creatorcontrib><title>An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><description>Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene
HNF4α
, directly represses the expression of the epithelial microRNAs
(miRs)-200c
and -
34a
, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4
α
, previously identified as a transcriptional repressor of
Snail
, induces the
miRs-34a
and -
200a, b, c
that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4
α
and miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Cycle Analysis</subject><subject>Cell Differentiation</subject><subject>Cellular Biology</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Hepatocyte Nuclear Factor 4</subject><subject>Hepatocyte Nuclear Factor 4 - deficiency</subject><subject>Hepatocyte Nuclear Factor 4 - genetics</subject><subject>Hepatocyte Nuclear Factor 4 - metabolism</subject><subject>Hepatocytes</subject><subject>Hepatocytes - metabolism</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Liver - cytology</subject><subject>Liver - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MicroRNAs</subject><subject>MicroRNAs - metabolism</subject><subject>Original Paper</subject><subject>Snail Family Transcription Factors</subject><subject>Stem Cells</subject><subject>Stem Cells - metabolism</subject><subject>Transcription Factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><issn>1350-9047</issn><issn>1476-5403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkstu1DAUhiMEoqWwY428ZEEGO3ZuG6RRRRmkUZG4rC3bOZmcKrGD7Qz0sXgBHoFnwtMp5SIkS7Z0Pv_H5_efZU8ZXTHKm5em61YFZWzF6vJedspEXeWloPx-OvOS5i0V9Un2KIQrSmlVt9XD7KQoGG8Zp6fZ97UlMGOIKqIhE1rMDXqzYPTXREP8AmBJHIBEr2wwHueIzpJemeh8IB-swpEo25HN5YX48Y0YZ6N3YyAj7sGTEGEiBsYjM8CsojPXEUgPKi4eAoGvg_MR7Y64eXYBU83DbhnVTZ-0DhIWQsjRDqjxBp3QePf-ch0eZw96NQZ4crufZZ8uXn883-Tbd2_enq-3uREVjbmqdVGXmndNZdqe8lJXfadE1wsOXHPBgHLFTMuTY53umgIUbUqlRaupbnXNz7JXR9150RN0BtKUapSzx0n5a-kUyr8rFge5c3vJefoLcRDIjwLDP9c2662cVRpy8ZLStqFMiD1L_PPbht59XiBEOWE4GKksuCVIln685FVT8IS-OKLJkxA89Hf6jMpDRGSKiDxERKaIJPzZn6Pcwb8y8fupIZXsDry8cou3yd7_C_4Ex23NjQ</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Garibaldi, F</creator><creator>Cicchini, C</creator><creator>Conigliaro, A</creator><creator>Santangelo, L</creator><creator>Cozzolino, A M</creator><creator>Grassi, G</creator><creator>Marchetti, A</creator><creator>Tripodi, M</creator><creator>Amicone, L</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>1XC</scope><scope>VOOES</scope><scope>5PM</scope></search><sort><creationdate>20120601</creationdate><title>An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs</title><author>Garibaldi, F ; Cicchini, C ; Conigliaro, A ; Santangelo, L ; Cozzolino, A M ; Grassi, G ; Marchetti, A ; Tripodi, M ; Amicone, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-a7b275b3d86c9f035b6fda4df43e3b341e03a1c93135dbd82ea085ab49b0b9b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Cycle Analysis</topic><topic>Cell Differentiation</topic><topic>Cellular Biology</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Hepatocyte Nuclear Factor 4</topic><topic>Hepatocyte Nuclear Factor 4 - deficiency</topic><topic>Hepatocyte Nuclear Factor 4 - genetics</topic><topic>Hepatocyte Nuclear Factor 4 - metabolism</topic><topic>Hepatocytes</topic><topic>Hepatocytes - metabolism</topic><topic>Life Sciences</topic><topic>Liver</topic><topic>Liver - cytology</topic><topic>Liver - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>MicroRNAs</topic><topic>MicroRNAs - metabolism</topic><topic>Original Paper</topic><topic>Snail Family Transcription Factors</topic><topic>Stem Cells</topic><topic>Stem Cells - metabolism</topic><topic>Transcription Factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garibaldi, F</creatorcontrib><creatorcontrib>Cicchini, C</creatorcontrib><creatorcontrib>Conigliaro, A</creatorcontrib><creatorcontrib>Santangelo, L</creatorcontrib><creatorcontrib>Cozzolino, A M</creatorcontrib><creatorcontrib>Grassi, G</creatorcontrib><creatorcontrib>Marchetti, A</creatorcontrib><creatorcontrib>Tripodi, M</creatorcontrib><creatorcontrib>Amicone, L</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>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garibaldi, F</au><au>Cicchini, C</au><au>Conigliaro, A</au><au>Santangelo, L</au><au>Cozzolino, A M</au><au>Grassi, G</au><au>Marchetti, A</au><au>Tripodi, M</au><au>Amicone, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>19</volume><issue>6</issue><spage>937</spage><epage>946</epage><pages>937-946</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene
HNF4α
, directly represses the expression of the epithelial microRNAs
(miRs)-200c
and -
34a
, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4
α
, previously identified as a transcriptional repressor of
Snail
, induces the
miRs-34a
and -
200a, b, c
that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4
α
and miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22139130</pmid><doi>10.1038/cdd.2011.175</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1350-9047 |
| ispartof | Cell death and differentiation, 2012-06, Vol.19 (6), p.937-946 |
| issn | 1350-9047 1476-5403 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3354047 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Apoptosis Biochemistry Biochemistry, Molecular Biology Biomedical and Life Sciences Cell Biology Cell Cycle Analysis Cell Differentiation Cellular Biology Epithelial-Mesenchymal Transition Hepatocyte Nuclear Factor 4 Hepatocyte Nuclear Factor 4 - deficiency Hepatocyte Nuclear Factor 4 - genetics Hepatocyte Nuclear Factor 4 - metabolism Hepatocytes Hepatocytes - metabolism Life Sciences Liver Liver - cytology Liver - metabolism Mice Mice, Knockout MicroRNAs MicroRNAs - metabolism Original Paper Snail Family Transcription Factors Stem Cells Stem Cells - metabolism Transcription Factors Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic |
| title | An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T12%3A04%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20epistatic%20mini-circuitry%20between%20the%20transcription%20factors%20Snail%20and%20HNF4%CE%B1%20controls%20liver%20stem%20cell%20and%20hepatocyte%20features%20exhorting%20opposite%20regulation%20on%20stemness-inhibiting%20microRNAs&rft.jtitle=Cell%20death%20and%20differentiation&rft.au=Garibaldi,%20F&rft.date=2012-06-01&rft.volume=19&rft.issue=6&rft.spage=937&rft.epage=946&rft.pages=937-946&rft.issn=1350-9047&rft.eissn=1476-5403&rft_id=info:doi/10.1038/cdd.2011.175&rft_dat=%3Cproquest_pubme%3E1011536823%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1011536823&rft_id=info:pmid/22139130&rfr_iscdi=true |