In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration
The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maint...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714003052 |
| _version_ | 1818848972782960640 |
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| author | Yuval Rinkevich Daniel T. Montoro Humberto Contreras-Trujillo Orit Harari-Steinberg Aaron M. Newman Jonathan M. Tsai Xinhong Lim Renee Van-Amerongen Angela Bowman Michael Januszyk Oren Pleniceanu Roel Nusse Michael T. Longaker Irving L. Weissman Benjamin Dekel |
| author_facet | Yuval Rinkevich Daniel T. Montoro Humberto Contreras-Trujillo Orit Harari-Steinberg Aaron M. Newman Jonathan M. Tsai Xinhong Lim Renee Van-Amerongen Angela Bowman Michael Januszyk Oren Pleniceanu Roel Nusse Michael T. Longaker Irving L. Weissman Benjamin Dekel |
| author_sort | Yuval Rinkevich |
| collection | DOAJ |
| description | The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs) into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life. |
| first_indexed | 2024-12-19T06:25:50Z |
| format | Article |
| id | doaj.art-5859db2fcb9a4aee8444a48bed517787 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T06:25:50Z |
| publishDate | 2014-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5859db2fcb9a4aee8444a48bed5177872022-12-21T20:32:34ZengElsevierCell Reports2211-12472014-05-01741270128310.1016/j.celrep.2014.04.018In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and RegenerationYuval Rinkevich0Daniel T. Montoro1Humberto Contreras-Trujillo2Orit Harari-Steinberg3Aaron M. Newman4Jonathan M. Tsai5Xinhong Lim6Renee Van-Amerongen7Angela Bowman8Michael Januszyk9Oren Pleniceanu10Roel Nusse11Michael T. Longaker12Irving L. Weissman13Benjamin Dekel14Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAHagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAPediatric Stem Cell Research Institute, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv 52621, IsraelStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAHagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USAPediatric Stem Cell Research Institute, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv 52621, IsraelStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAPediatric Stem Cell Research Institute, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv 52621, IsraelThe mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs) into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.http://www.sciencedirect.com/science/article/pii/S2211124714003052 |
| spellingShingle | Yuval Rinkevich Daniel T. Montoro Humberto Contreras-Trujillo Orit Harari-Steinberg Aaron M. Newman Jonathan M. Tsai Xinhong Lim Renee Van-Amerongen Angela Bowman Michael Januszyk Oren Pleniceanu Roel Nusse Michael T. Longaker Irving L. Weissman Benjamin Dekel In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration Cell Reports |
| title | In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration |
| title_full | In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration |
| title_fullStr | In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration |
| title_full_unstemmed | In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration |
| title_short | In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration |
| title_sort | in vivo clonal analysis reveals lineage restricted progenitor characteristics in mammalian kidney development maintenance and regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714003052 |
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