Single cell analysis of the developing mouse kidney provides deeper insight into marker gene expression and ligand-receptor crosstalk
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Recent advances in the generation of kidney organoids and the culture of primary nephron progenitors from mouse and human have been based on knowledge of the molecular basis of kidney development in mice. Although gene expression during kidney development has been intensely investigated, single cell profiling provides new opportunities to further subsect component cell types and the signalling networks at play. Here, we describe the generation and analysis of 6732 single cell transcriptomes from the fetal mouse kidney [embryonic day (E)18.5] and 7853 sorted nephron progenitor cells (E14.5). These datasets provide improved resolution of cell types and specific markers, including subdivision of the renal stroma and heterogeneity within the nephron progenitor population. Ligand-receptor interaction and pathway analysis reveals novel crosstalk between cellular compartments and associates new pathways with differentiation of nephron and ureteric epithelium cell types. We identify transcriptional congruence between the distal nephron and ureteric epithelium, showing that most markers previously used to identify ureteric epithelium are not specific. Together, this work improves our understanding of metanephric kidney development and provides a template to guide the regeneration of renal tissue.
Citation
@article{n_combes2019,
author = {N Combes, Alexander and Phipson, Belinda and T Lawlor, Kynan
and Dorison, Aude and Patrick, Ralph and Zappia, Luke and P Harvey,
Richard and Oshlack, Alicia and H Little, Melissa},
title = {Single Cell Analysis of the Developing Mouse Kidney Provides
Deeper Insight into Marker Gene Expression and Ligand-Receptor
Crosstalk},
journal = {Development},
volume = {146},
number = {12},
date = {2019-06-01},
url = {https://doi.org/10.1242/dev.178673},
doi = {10.1242/dev.178673},
issn = {0950-1991, 1477-9129},
langid = {en},
abstract = {Recent advances in the generation of kidney organoids and
the culture of primary nephron progenitors from mouse and human have
been based on knowledge of the molecular basis of kidney development
in mice. Although gene expression during kidney development has been
intensely investigated, single cell profiling provides new
opportunities to further subsect component cell types and the
signalling networks at play. Here, we describe the generation and
analysis of 6732 single cell transcriptomes from the fetal mouse
kidney {[}embryonic day (E)18.5{]} and 7853 sorted nephron
progenitor cells (E14.5). These datasets provide improved resolution
of cell types and specific markers, including subdivision of the
renal stroma and heterogeneity within the nephron progenitor
population. Ligand-receptor interaction and pathway analysis reveals
novel crosstalk between cellular compartments and associates new
pathways with differentiation of nephron and ureteric epithelium
cell types. We identify transcriptional congruence between the
distal nephron and ureteric epithelium, showing that most markers
previously used to identify ureteric epithelium are not specific.
Together, this work improves our understanding of metanephric kidney
development and provides a template to guide the regeneration of
renal tissue.}
}