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
Hauptverfasser: Brown, Aaron C., Muthukrishnan, Sree Deepthi, Oxburgh, Leif
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container_title Developmental cell
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creator Brown, Aaron C.
Muthukrishnan, Sree Deepthi
Oxburgh, Leif
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.
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inhibitors</topic><topic>Smad1 Protein - metabolism</topic><topic>Smad5 Protein - antagonists &amp; 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. 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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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