Human kidney clonal proliferation disclose lineage-restricted precursor characteristics

Abstract In-vivo single cell clonal analysis in the adult mouse kidney has previously shown lineage-restricted clonal proliferation within varying nephron segments as a mechanism responsible for cell replacement and local regeneration. To analyze ex-vivo clonal growth, we now preformed limiting dilu...

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Autores principales:	Cohen-Zontag Osnat, Gershon Rotem, Harari-Steinberg Orit, Kanter Itamar, Omer Dorit, Pleniceanu Oren, Tam Gal, Oriel Sarit, Ben Hur Herzel, Katz Guy, Zohar Dotan, Kalisky Tomer, Dekel Benjamin, Pode-Shakked Naomi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a01fffd07da7466cb1f955cb3c170fba
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spelling	oai:doaj.org-article:a01fffd07da7466cb1f955cb3c170fba2021-12-02T12:42:18ZHuman kidney clonal proliferation disclose lineage-restricted precursor characteristics10.1038/s41598-020-78366-32045-2322https://doaj.org/article/a01fffd07da7466cb1f955cb3c170fba2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78366-3https://doaj.org/toc/2045-2322Abstract In-vivo single cell clonal analysis in the adult mouse kidney has previously shown lineage-restricted clonal proliferation within varying nephron segments as a mechanism responsible for cell replacement and local regeneration. To analyze ex-vivo clonal growth, we now preformed limiting dilution to generate genuine clonal cultures from one single human renal epithelial cell, which can give rise to up to 3.4 * 106 cells, and analyzed their characteristics using transcriptomics. A comparison between clonal cultures revealed restriction to either proximal or distal kidney sub-lineages with distinct cellular and molecular characteristics; rapidly amplifying de-differentiated clones and a stably proliferating cuboidal epithelial-appearing clones, respectively. Furthermore, each showed distinct molecular features including cell-cycle, epithelial-mesenchymal transition, oxidative phosphorylation, BMP signaling pathway and cell surface markers. In addition, analysis of clonal versus bulk cultures show early clones to be more quiescent, with elevated expression of renal developmental genes and overall reduction in renal identity markers, but with an overlapping expression of nephron segment identifiers and multiple identity. Thus, ex-vivo clonal growth mimics the in-vivo situation displaying lineage-restricted precursor characteristics of mature renal cells. These data suggest that for reconstruction of varying renal lineages with human adult kidney based organoid technology and kidney regeneration ex-vivo, use of multiple heterogeneous precursors is warranted.Cohen-Zontag OsnatGershon RotemHarari-Steinberg OritKanter ItamarOmer DoritPleniceanu OrenTam GalOriel SaritBen Hur HerzelKatz GuyZohar DotanKalisky TomerDekel BenjaminPode-Shakked NaomiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cohen-Zontag Osnat Gershon Rotem Harari-Steinberg Orit Kanter Itamar Omer Dorit Pleniceanu Oren Tam Gal Oriel Sarit Ben Hur Herzel Katz Guy Zohar Dotan Kalisky Tomer Dekel Benjamin Pode-Shakked Naomi Human kidney clonal proliferation disclose lineage-restricted precursor characteristics
description	Abstract In-vivo single cell clonal analysis in the adult mouse kidney has previously shown lineage-restricted clonal proliferation within varying nephron segments as a mechanism responsible for cell replacement and local regeneration. To analyze ex-vivo clonal growth, we now preformed limiting dilution to generate genuine clonal cultures from one single human renal epithelial cell, which can give rise to up to 3.4 * 106 cells, and analyzed their characteristics using transcriptomics. A comparison between clonal cultures revealed restriction to either proximal or distal kidney sub-lineages with distinct cellular and molecular characteristics; rapidly amplifying de-differentiated clones and a stably proliferating cuboidal epithelial-appearing clones, respectively. Furthermore, each showed distinct molecular features including cell-cycle, epithelial-mesenchymal transition, oxidative phosphorylation, BMP signaling pathway and cell surface markers. In addition, analysis of clonal versus bulk cultures show early clones to be more quiescent, with elevated expression of renal developmental genes and overall reduction in renal identity markers, but with an overlapping expression of nephron segment identifiers and multiple identity. Thus, ex-vivo clonal growth mimics the in-vivo situation displaying lineage-restricted precursor characteristics of mature renal cells. These data suggest that for reconstruction of varying renal lineages with human adult kidney based organoid technology and kidney regeneration ex-vivo, use of multiple heterogeneous precursors is warranted.
format	article
author	Cohen-Zontag Osnat Gershon Rotem Harari-Steinberg Orit Kanter Itamar Omer Dorit Pleniceanu Oren Tam Gal Oriel Sarit Ben Hur Herzel Katz Guy Zohar Dotan Kalisky Tomer Dekel Benjamin Pode-Shakked Naomi
author_facet	Cohen-Zontag Osnat Gershon Rotem Harari-Steinberg Orit Kanter Itamar Omer Dorit Pleniceanu Oren Tam Gal Oriel Sarit Ben Hur Herzel Katz Guy Zohar Dotan Kalisky Tomer Dekel Benjamin Pode-Shakked Naomi
author_sort	Cohen-Zontag Osnat
title	Human kidney clonal proliferation disclose lineage-restricted precursor characteristics
title_short	Human kidney clonal proliferation disclose lineage-restricted precursor characteristics
title_full	Human kidney clonal proliferation disclose lineage-restricted precursor characteristics
title_fullStr	Human kidney clonal proliferation disclose lineage-restricted precursor characteristics
title_full_unstemmed	Human kidney clonal proliferation disclose lineage-restricted precursor characteristics
title_sort	human kidney clonal proliferation disclose lineage-restricted precursor characteristics
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/a01fffd07da7466cb1f955cb3c170fba
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Human kidney clonal proliferation disclose lineage-restricted precursor characteristics

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