A Synthetic Niche for Nephron Progenitor Cells
FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fo...
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Veröffentlicht in: | Developmental cell 2015-07, Vol.34 (2), p.229-241 |
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description | FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fold in this environment can be induced to form tubules expressing nephron differentiation markers. Single-cell culture reveals phenotypic variability within the early CITED1-expressing NPC compartment, indicating that it is a mixture of cells with varying progenitor potential. Furthermore, we find that the developmental age of NPCs does not correlate with propagation capacity, indicating that cessation of nephrogenesis is related to factors other than an intrinsic clock. This in vitro nephron progenitor niche will have important applications for expansion of cells for engraftment and will facilitate investigation of mechanisms that determine the balance between renewal and differentiation in these cells.
[Display omitted]
•NPCs are enzymatically liberated from embryonic kidneys•NPCs are purified from other cells in the niche by magnetic depletion•NPC expansion medium provides niche signals for undifferentiated proliferation•NPCs expanded in NPEM form nephron tubules when cultured in organotypic conditions
The embryonic mammalian kidney maintains nephron progenitor cells (NPCs) within a specific niche. Niche signals have been recapitulated in culture, allowing many million-fold expansion of NPCs. NPC propagation facilitates investigation of mechanisms governing their proliferation and differentiation and provides sufficient cell numbers to generate kidney tissue in vitro. |
doi_str_mv | 10.1016/j.devcel.2015.06.021 |
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[Display omitted]
•NPCs are enzymatically liberated from embryonic kidneys•NPCs are purified from other cells in the niche by magnetic depletion•NPC expansion medium provides niche signals for undifferentiated proliferation•NPCs expanded in NPEM form nephron tubules when cultured in organotypic conditions
The embryonic mammalian kidney maintains nephron progenitor cells (NPCs) within a specific niche. Niche signals have been recapitulated in culture, allowing many million-fold expansion of NPCs. NPC propagation facilitates investigation of mechanisms governing their proliferation and differentiation and provides sufficient cell numbers to generate kidney tissue in vitro.</description><identifier>ISSN: 1534-5807</identifier><identifier>EISSN: 1878-1551</identifier><identifier>DOI: 10.1016/j.devcel.2015.06.021</identifier><identifier>PMID: 26190145</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Bone Morphogenetic Proteins - metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Embryonic Stem Cells - cytology ; Enzyme Activation ; Fibroblast Growth Factors - metabolism ; Homeodomain Proteins - biosynthesis ; Homeodomain Proteins - genetics ; Mice ; Mice, Inbred ICR ; Mice, Transgenic ; Nephrons - cytology ; Nephrons - embryology ; Nuclear Proteins - biosynthesis ; Nuclear Proteins - genetics ; Organogenesis ; Pyrazoles - pharmacology ; Pyrimidines - pharmacology ; Smad1 Protein - antagonists & inhibitors ; Smad1 Protein - metabolism ; Smad5 Protein - antagonists & inhibitors ; Smad5 Protein - metabolism ; Trans-Activators - biosynthesis ; Trans-Activators - genetics ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Wnt Proteins - metabolism</subject><ispartof>Developmental cell, 2015-07, Vol.34 (2), p.229-241</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c599t-c06d30b537dec123e7d477b0bebc9a3058d073ee3d6e51ef5f360253fd91e5453</citedby><cites>FETCH-LOGICAL-c599t-c06d30b537dec123e7d477b0bebc9a3058d073ee3d6e51ef5f360253fd91e5453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.devcel.2015.06.021$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,782,786,887,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26190145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brown, Aaron C.</creatorcontrib><creatorcontrib>Muthukrishnan, Sree Deepthi</creatorcontrib><creatorcontrib>Oxburgh, Leif</creatorcontrib><title>A Synthetic Niche for Nephron Progenitor Cells</title><title>Developmental cell</title><addtitle>Dev Cell</addtitle><description>FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fold in this environment can be induced to form tubules expressing nephron differentiation markers. Single-cell culture reveals phenotypic variability within the early CITED1-expressing NPC compartment, indicating that it is a mixture of cells with varying progenitor potential. Furthermore, we find that the developmental age of NPCs does not correlate with propagation capacity, indicating that cessation of nephrogenesis is related to factors other than an intrinsic clock. This in vitro nephron progenitor niche will have important applications for expansion of cells for engraftment and will facilitate investigation of mechanisms that determine the balance between renewal and differentiation in these cells.
[Display omitted]
•NPCs are enzymatically liberated from embryonic kidneys•NPCs are purified from other cells in the niche by magnetic depletion•NPC expansion medium provides niche signals for undifferentiated proliferation•NPCs expanded in NPEM form nephron tubules when cultured in organotypic conditions
The embryonic mammalian kidney maintains nephron progenitor cells (NPCs) within a specific niche. Niche signals have been recapitulated in culture, allowing many million-fold expansion of NPCs. NPC propagation facilitates investigation of mechanisms governing their proliferation and differentiation and provides sufficient cell numbers to generate kidney tissue in vitro.</description><subject>Animals</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Enzyme Activation</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Homeodomain Proteins - biosynthesis</subject><subject>Homeodomain Proteins - genetics</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Mice, Transgenic</subject><subject>Nephrons - cytology</subject><subject>Nephrons - embryology</subject><subject>Nuclear Proteins - biosynthesis</subject><subject>Nuclear Proteins - genetics</subject><subject>Organogenesis</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Smad1 Protein - antagonists & inhibitors</subject><subject>Smad1 Protein - metabolism</subject><subject>Smad5 Protein - antagonists & inhibitors</subject><subject>Smad5 Protein - metabolism</subject><subject>Trans-Activators - biosynthesis</subject><subject>Trans-Activators - genetics</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Wnt Proteins - metabolism</subject><issn>1534-5807</issn><issn>1878-1551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMofv8DkR69tM40TdNeBFn8AlFBPYc2mbpZus2adBf890bWz4unGWbmfWfmYewIIUPA8nSWGVpp6rMcUGRQZpDjBtvFSlYpCoGbMRe8SEUFcofthTCDKMMKttlOXmINWIhdlp0nj2_DOKXR6uTO6iklnfPJHS2m3g3Jg3cvNNgxlibU9-GAbXVNH-jwM-6z58uLp8l1ent_dTM5v021qOsx1VAaDq3g0pDGnJM0hZQttNTquuEgKgOSE3FTkkDqRMdLyAXvTI0kCsH32dnad7Fs52Q0DaNverXwdt74N-Uaq_52BjtVL26lCoF1kctocPJp4N3rksKo5jZEWn0zkFsGhRKA84LXGEeL9aj2LgRP3fcaBPWBWs3UGrX6QK2gVBF1lB3_PvFb9MX25weKoFaWvAra0qDJWE96VMbZ_ze8A47ikTs</recordid><startdate>20150727</startdate><enddate>20150727</enddate><creator>Brown, Aaron C.</creator><creator>Muthukrishnan, Sree Deepthi</creator><creator>Oxburgh, Leif</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20150727</creationdate><title>A Synthetic Niche for Nephron Progenitor Cells</title><author>Brown, Aaron C. ; Muthukrishnan, Sree Deepthi ; Oxburgh, Leif</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c599t-c06d30b537dec123e7d477b0bebc9a3058d073ee3d6e51ef5f360253fd91e5453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Enzyme Activation</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Homeodomain Proteins - biosynthesis</topic><topic>Homeodomain Proteins - genetics</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Mice, Transgenic</topic><topic>Nephrons - cytology</topic><topic>Nephrons - embryology</topic><topic>Nuclear Proteins - biosynthesis</topic><topic>Nuclear Proteins - genetics</topic><topic>Organogenesis</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrimidines - pharmacology</topic><topic>Smad1 Protein - antagonists & inhibitors</topic><topic>Smad1 Protein - metabolism</topic><topic>Smad5 Protein - antagonists & inhibitors</topic><topic>Smad5 Protein - metabolism</topic><topic>Trans-Activators - biosynthesis</topic><topic>Trans-Activators - genetics</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, Aaron C.</creatorcontrib><creatorcontrib>Muthukrishnan, Sree Deepthi</creatorcontrib><creatorcontrib>Oxburgh, Leif</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Developmental cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, Aaron C.</au><au>Muthukrishnan, Sree Deepthi</au><au>Oxburgh, Leif</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Synthetic Niche for Nephron Progenitor Cells</atitle><jtitle>Developmental cell</jtitle><addtitle>Dev Cell</addtitle><date>2015-07-27</date><risdate>2015</risdate><volume>34</volume><issue>2</issue><spage>229</spage><epage>241</epage><pages>229-241</pages><issn>1534-5807</issn><eissn>1878-1551</eissn><abstract>FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fold in this environment can be induced to form tubules expressing nephron differentiation markers. Single-cell culture reveals phenotypic variability within the early CITED1-expressing NPC compartment, indicating that it is a mixture of cells with varying progenitor potential. Furthermore, we find that the developmental age of NPCs does not correlate with propagation capacity, indicating that cessation of nephrogenesis is related to factors other than an intrinsic clock. This in vitro nephron progenitor niche will have important applications for expansion of cells for engraftment and will facilitate investigation of mechanisms that determine the balance between renewal and differentiation in these cells.
[Display omitted]
•NPCs are enzymatically liberated from embryonic kidneys•NPCs are purified from other cells in the niche by magnetic depletion•NPC expansion medium provides niche signals for undifferentiated proliferation•NPCs expanded in NPEM form nephron tubules when cultured in organotypic conditions
The embryonic mammalian kidney maintains nephron progenitor cells (NPCs) within a specific niche. Niche signals have been recapitulated in culture, allowing many million-fold expansion of NPCs. NPC propagation facilitates investigation of mechanisms governing their proliferation and differentiation and provides sufficient cell numbers to generate kidney tissue in vitro.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26190145</pmid><doi>10.1016/j.devcel.2015.06.021</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bone Morphogenetic Proteins - metabolism Cell Differentiation Cell Proliferation Cells, Cultured Embryonic Stem Cells - cytology Enzyme Activation Fibroblast Growth Factors - metabolism Homeodomain Proteins - biosynthesis Homeodomain Proteins - genetics Mice Mice, Inbred ICR Mice, Transgenic Nephrons - cytology Nephrons - embryology Nuclear Proteins - biosynthesis Nuclear Proteins - genetics Organogenesis Pyrazoles - pharmacology Pyrimidines - pharmacology Smad1 Protein - antagonists & inhibitors Smad1 Protein - metabolism Smad5 Protein - antagonists & inhibitors Smad5 Protein - metabolism Trans-Activators - biosynthesis Trans-Activators - genetics Transcription Factors - biosynthesis Transcription Factors - genetics Wnt Proteins - metabolism |
title | A Synthetic Niche for Nephron Progenitor Cells |
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