Fount, fate, features, and function of renal erythropoietin-producing cells
Renal erythropoietin (Epo)-producing (REP) cells represent a rare and incompletely understood cell type. REP cells are fibroblast-like cells located in close proximity to blood vessels and tubules of the corticomedullary border region. Epo mRNA in REP cells is produced in a pronounced “on–off” mode,...
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| Veröffentlicht in: | Pflügers Archiv 2022-08, Vol.474 (8), p.783-797 |
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| creator | Dahl, Sophie L. Bapst, Andreas M. Khodo, Stellor Nlandu Scholz, Carsten C. Wenger, Roland H. |
| description | Renal erythropoietin (Epo)-producing (REP) cells represent a rare and incompletely understood cell type. REP cells are fibroblast-like cells located in close proximity to blood vessels and tubules of the corticomedullary border region. Epo mRNA in REP cells is produced in a pronounced “on–off” mode, showing transient transcriptional bursts upon exposure to hypoxia. In contrast to “ordinary” fibroblasts, REP cells do not proliferate ex vivo, cease to produce Epo, and lose their identity following immortalization and prolonged in vitro culture, consistent with the loss of Epo production following REP cell proliferation during tissue remodelling in chronic kidney disease. Because Epo protein is usually not detectable in kidney tissue, and Epo mRNA is only transiently induced under hypoxic conditions, transgenic mouse models have been developed to permanently label REP cell precursors, active Epo producers, and inactive descendants. Future single-cell analyses of the renal stromal compartment will identify novel characteristic markers of tagged REP cells, which will provide novel insights into the regulation of Epo expression in this unique cell type. |
| doi_str_mv | 10.1007/s00424-022-02714-7 |
| format | Article |
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REP cells are fibroblast-like cells located in close proximity to blood vessels and tubules of the corticomedullary border region. Epo mRNA in REP cells is produced in a pronounced “on–off” mode, showing transient transcriptional bursts upon exposure to hypoxia. In contrast to “ordinary” fibroblasts, REP cells do not proliferate ex vivo, cease to produce Epo, and lose their identity following immortalization and prolonged in vitro culture, consistent with the loss of Epo production following REP cell proliferation during tissue remodelling in chronic kidney disease. Because Epo protein is usually not detectable in kidney tissue, and Epo mRNA is only transiently induced under hypoxic conditions, transgenic mouse models have been developed to permanently label REP cell precursors, active Epo producers, and inactive descendants. Future single-cell analyses of the renal stromal compartment will identify novel characteristic markers of tagged REP cells, which will provide novel insights into the regulation of Epo expression in this unique cell type.</description><identifier>ISSN: 0031-6768</identifier><identifier>ISSN: 1432-2013</identifier><identifier>EISSN: 1432-2013</identifier><identifier>DOI: 10.1007/s00424-022-02714-7</identifier><identifier>PMID: 35750861</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Anemia ; Animal models ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Blood ; Blood vessels ; Cell Biology ; Cell culture ; Cell proliferation ; Congenital diseases ; Erythropoietin ; Erythropoietin - metabolism ; Fibroblasts ; Gene expression ; Homeostasis ; Human Physiology ; Hypoxia ; Hypoxia - metabolism ; Immortalization ; Invited Review ; Iron ; Kidney - metabolism ; Kidney diseases ; Kidneys ; Liver ; Mice ; Mice, Transgenic ; Molecular Medicine ; Mutation ; Neurosciences ; Physiology ; Proteins ; Receptors ; Renal function ; Renal Insufficiency, Chronic - metabolism ; RNA, Messenger - metabolism ; Rodents ; Transcription factors ; Transgenic mice ; Tubules</subject><ispartof>Pflügers Archiv, 2022-08, Vol.474 (8), p.783-797</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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REP cells are fibroblast-like cells located in close proximity to blood vessels and tubules of the corticomedullary border region. Epo mRNA in REP cells is produced in a pronounced “on–off” mode, showing transient transcriptional bursts upon exposure to hypoxia. In contrast to “ordinary” fibroblasts, REP cells do not proliferate ex vivo, cease to produce Epo, and lose their identity following immortalization and prolonged in vitro culture, consistent with the loss of Epo production following REP cell proliferation during tissue remodelling in chronic kidney disease. Because Epo protein is usually not detectable in kidney tissue, and Epo mRNA is only transiently induced under hypoxic conditions, transgenic mouse models have been developed to permanently label REP cell precursors, active Epo producers, and inactive descendants. Future single-cell analyses of the renal stromal compartment will identify novel characteristic markers of tagged REP cells, which will provide novel insights into the regulation of Epo expression in this unique cell type.</description><subject>Anemia</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood</subject><subject>Blood vessels</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Cell proliferation</subject><subject>Congenital diseases</subject><subject>Erythropoietin</subject><subject>Erythropoietin - metabolism</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Homeostasis</subject><subject>Human Physiology</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Immortalization</subject><subject>Invited Review</subject><subject>Iron</subject><subject>Kidney - metabolism</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Liver</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular Medicine</subject><subject>Mutation</subject><subject>Neurosciences</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Renal function</subject><subject>Renal Insufficiency, Chronic - 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| subjects | Anemia Animal models Animals Biomedical and Life Sciences Biomedicine Blood Blood vessels Cell Biology Cell culture Cell proliferation Congenital diseases Erythropoietin Erythropoietin - metabolism Fibroblasts Gene expression Homeostasis Human Physiology Hypoxia Hypoxia - metabolism Immortalization Invited Review Iron Kidney - metabolism Kidney diseases Kidneys Liver Mice Mice, Transgenic Molecular Medicine Mutation Neurosciences Physiology Proteins Receptors Renal function Renal Insufficiency, Chronic - metabolism RNA, Messenger - metabolism Rodents Transcription factors Transgenic mice Tubules |
| title | Fount, fate, features, and function of renal erythropoietin-producing cells |
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