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 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..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Scientific Reports - 10(2020), 1, Seite 11 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cohen-Zontag Osnat [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1038/s41598-020-78366-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ059799455 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ059799455 | ||
| 003 | DE-627 | ||
| 005 | 20230501192423.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230228s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41598-020-78366-3 |2 doi | |
| 035 | |a (DE-627)DOAJ059799455 | ||
| 035 | |a (DE-599)DOAJa01fffd07da7466cb1f955cb3c170fba | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 0 | |a Cohen-Zontag Osnat |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human kidney clonal proliferation disclose lineage-restricted precursor characteristics |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a 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. | ||
| 653 | 0 | |a Medicine | |
| 653 | 0 | |a R | |
| 653 | 0 | |a Science | |
| 653 | 0 | |a Q | |
| 700 | 0 | |a Gershon Rotem |e verfasserin |4 aut | |
| 700 | 0 | |a Harari-Steinberg Orit |e verfasserin |4 aut | |
| 700 | 0 | |a Kanter Itamar |e verfasserin |4 aut | |
| 700 | 0 | |a Omer Dorit |e verfasserin |4 aut | |
| 700 | 0 | |a Pleniceanu Oren |e verfasserin |4 aut | |
| 700 | 0 | |a Tam Gal |e verfasserin |4 aut | |
| 700 | 0 | |a Oriel Sarit |e verfasserin |4 aut | |
| 700 | 0 | |a Ben Hur Herzel |e verfasserin |4 aut | |
| 700 | 0 | |a Katz Guy |e verfasserin |4 aut | |
| 700 | 0 | |a Zohar Dotan |e verfasserin |4 aut | |
| 700 | 0 | |a Kalisky Tomer |e verfasserin |4 aut | |
| 700 | 0 | |a Dekel Benjamin |e verfasserin |4 aut | |
| 700 | 0 | |a Pode-Shakked Naomi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Scientific Reports |d Nature Portfolio, 2011 |g 10(2020), 1, Seite 11 |w (DE-627)DOAJ000049077 |x 20452322 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2020 |g number:1 |g pages:11 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41598-020-78366-3 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/a01fffd07da7466cb1f955cb3c170fba |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41598-020-78366-3 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2045-2322 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2020 |e 1 |h 11 | ||