Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts
- Columbia University, United States
- Max Delbruck Center for Molecular Medicine, Germany
Abstract
Although most nephron segments contain one type of epithelial cell, the collecting ducts consists of at least two: intercalated (IC) and principal (PC) cells, which regulate acid-base and salt-water homeostasis, respectively. In adult kidneys, these cells are organized in rosettes suggesting functional interactions. Genetic studies in mouse revealed that transcription factor Tfcp2l1 coordinates IC and PC development. Tfcp2l1 induces the expression of IC specific genes, including specific H+-ATPase subunits and Jag1. Jag1 in turn, initiates Notch signaling in PCs but inhibits Notch signaling in ICs. Tfcp2l1 inactivation deletes ICs, whereas Jag1 inactivation results in the forfeiture of discrete IC and PC identities. Thus, Tfcp2l1 is a critical regulator of IC-PC patterning, acting cell-autonomously in ICs, and non-cell-autonomously in PCs. As a result, Tfcp2l1 regulates the diversification of cell types which is the central characteristic of 'salt and pepper' epithelia and distinguishes the collecting duct from all other nephron segments.
Data availability
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Identification of Tfcp2l1 target genes in the mouse kidneyPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87769).
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Tfcp2l1 controls cellular patterning of the collecting duct.Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE85325).
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RNA-Seq Gene Expression Analysis in Rat Metanephric Mesenchyme overexpressing Transcription Factor Tfcp2l1Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE87744).
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Genome wide map of Tfcp2l1 binding sites from mouse kidneyPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87752).
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Mapping of transcription factor binding sites in mouse embryonic stem cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE11431).
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Gene expression in epithelial and non-epithelial cells of renal originPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE24295).
Article and author information
Author details
Funding
National Institutes of Health (RO1DK073462)
- Jonathan Barasch
March of Dimes Foundation (Research Grant)
- Jonathan Barasch
National Institutes of Health (RO1DK092684)
- Jonathan Barasch
National Institutes of Health (U54DK104309)
- Jonathan Barasch
Deutsche Forschungsgemeinschaft (FOR 1368 FOR667 Emmy Noether)
- Kai M Schmidt-Ott
Urological Research Foundation Berlin
- Kai M Schmidt-Ott
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at Columbia. Protocol # AC-AAAH7404.
Reviewing Editor
- Roy Zent, Vanderbilt University Medical Center, United States
Publication history
- Received: December 19, 2016
- Accepted: June 3, 2017
- Accepted Manuscript published: June 3, 2017 (version 1)
- Accepted Manuscript updated: June 13, 2017 (version 2)
- Version of Record published: June 26, 2017 (version 3)
- Version of Record updated: June 27, 2017 (version 4)
Copyright
© 2017, Werth et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts
eLife 6:e24265.
https://doi.org/10.7554/eLife.24265
Further reading
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Following acute injury, the capillary vascular bed in the lung must be repaired to reestablish gas exchange with the external environment. Little is known about the transcriptional and signaling factors that drive pulmonary endothelial cell (EC) proliferation and subsequent regeneration of pulmonary capillaries, as well as their response to stress. Here, we show that the transcription factor Atf3 is essential for the regenerative response of the mouse pulmonary endothelium after influenza infection. Atf3 expression defines a subpopulation of capillary ECs enriched in genes involved in endothelial development, differentiation, and migration. During lung alveolar regeneration, this EC population expands and increases the expression of genes involved in angiogenesis, blood vessel development, and cellular response to stress. Importantly, endothelial cell-specific loss of Atf3 results in defective alveolar regeneration, in part through increased apoptosis and decreased proliferation in the endothelium. This leads to the general loss of alveolar endothelium and persistent morphological changes to the alveolar niche, including an emphysema-like phenotype with enlarged alveolar airspaces lined with regions that lack vascular investment. Taken together, these data implicate Atf3 as an essential component of the vascular response to acute lung injury that is required for successful lung alveolar regeneration.
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African trypanosomes proliferate as bloodstream forms (BSFs) and procyclic forms in the mammal and tsetse fly midgut, respectively. This allows them to colonise the host environment upon infection and ensure life cycle progression. Yet, understanding of the mechanisms that regulate and drive the cell replication cycle of these forms is limited. Using single-cell transcriptomics on unsynchronised cell populations, we have obtained high resolution cell cycle regulated (CCR) transcriptomes of both procyclic and slender BSF Trypanosoma brucei without prior cell sorting or synchronisation. Additionally, we describe an efficient freeze–thawing protocol that allows single-cell transcriptomic analysis of cryopreserved T. brucei. Computational reconstruction of the cell cycle using periodic pseudotime inference allowed the dynamic expression patterns of cycling genes to be profiled for both life cycle forms. Comparative analyses identify a core cycling transcriptome highly conserved between forms, as well as several genes where transcript levels dynamics are form specific. Comparing transcript expression patterns with protein abundance revealed that the majority of genes with periodic cycling transcript and protein levels exhibit a relative delay between peak transcript and protein expression. This work reveals novel detail of the CCR transcriptomes of both forms, which are available for further interrogation via an interactive webtool.
