Dataset Information

Kidney collecting duct cell type composition is regulated by Notch signaling via modulation of mTORC1 activity (ChIP-Seq)

ABSTRACT: The kidneys play an essential role in water and electrolyte homeostasis that is dependent on maintenance of intermingled epithelial cell types within tubular collecting duct segments. Notch signaling, a regulator of cell fate selection, ensures urine concentrating capacity in adult organisms by preventing water reabsorbing principal cell types in the kidney collecting duct segments from converting into mitochondria rich intercalated cell types. Here we identify that Hes1, a target of Notch signaling, allows for the maintenance of functionally different epithelial cell types with differing metabolic states within the same microenvironment by regulating mechanistic target of rapamycin complex 1 (mTORC1) activity. Hes1 directly represses mTOR pathway components, such as Irs1, and suppresses mTORC1 activity in principal cells. Increasing mTORC1 activity in mature principal cells is sufficient to initiate the acquisition of intercalated cell type properties. These findings reveal that diversity of mature epithelial cell types within collecting duct segments is dependent on the level of mTORC1 activity, and likely allows for the epithelial cell type plasticity to be regulated by physiologic cues and the ability to sense and transduce metabolic cues.

ORGANISM(S): Mus musculus

PROVIDER: GSE260472 | GEO | 2026/08/09

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Purpose: Transport processes in the renal collecting duct are responsible for precise regulation of blood pressure and body fluid composition. The collecting duct is composed of at least three cell types, type A intercalated cells (A-IC), type B intercalated cells (B-IC) and principal cells (PC). To identify the genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters and secreted proteins, we used cell surface markers necessary for isolation of each of the three cell types using fluorescence-activated cell sorting and carried out single-cell RNA-Seq to measure the mRNA species in each of these cell types. Methods: We enriched each of the three cell types using fluorescence-activated cell sorting. Subsequently, we carried out single-cell RNA-Seq of those cells using a microfluidic chip (Fluidigm C1 system). Single-cell cDNA libraries were constructed for paired-end sequencing and sequenced on Illumina HiSeq3000 platform. In addition, we also microdissected mouse CCDs and cTALs and carried out single-tubule RNA-Seq. Reads were mapped to mouse Ensembl Genome by STAR and transcript abundances were calculated in the units of transcripts per million (TPM) using RSEM (https://github.com/deweylab/RSEM). Single-cell RNA-Seq data anaysis were carried out using Seurat package in R. Results and conclusion: Single-cell cDNA libraries were constructed for paired-end sequencing and at least 10-million sequence reads per cell were mapped to the mouse genome (Ensembl, GRCm38.p5). On average, cells were sequenced to a depth of 3000 genes (TPM>1). Unsupervised clustering analysis revealed five different cell types, namely type A intercalated cells (n=87), type B intercalated cells (n=23), principal cells (74), proximal tubule cells (n=19), and non-epithelial cells (n=32). The identified patterns of gene expression among A-ICs, B-ICs and PCs provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.

Dataset Information

Kidney collecting duct cell type composition is regulated by Notch signaling via modulation of mTORC1 activity (ChIP-Seq)

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets