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Single-cell analysis of progenitor cell dynamics and lineage specification of the human fetal kidney

ABSTRACT: Single-cell analysis of progenitor cell dynamics and lineage specification of the human fetal kidney

PROVIDER: PRJNA430106 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6495640_1.fastq.gz	Fastqsanger.gz
	SRR6495640_2.fastq.gz	Fastqsanger.gz
	SRR6495641_1.fastq.gz	Fastqsanger.gz
	SRR6495641_2.fastq.gz	Fastqsanger.gz
	SRR6495639_1.fastq.gz	Fastqsanger.gz

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Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney.

Project description:The mammalian kidney develops through reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons. Most of our knowledge of the developmental regulators driving this process arises from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories during development. Single-cell transcriptome analyses of 6414 cells from five individual specimens identified 11 initial clusters of specific renal cell types as defined by their gene expression profile. Further subclustering identifies progenitors, and mature and intermediate stages of differentiation for several renal lineages. Other lineages identified include mesangium, stroma, endothelial and immune cells. Novel markers for these cell types were revealed in the analysis, as were components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression profile of the developing human kidney at the single-cell level.

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Single-cell analysis of progenitor cell dynamics and lineage specification of the human fetal kidney

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Project description:Emerging evidence is revealing critical roles of intracellular pH (pHi) in development (), but it remains unclear whether pHi regulates adult stem cell lineage specification. We find that pHi dynamics is a key regulator of cell fate in the mouse intestinal stem cell (ISC) lineage. We identify a pHi gradient along the crypt axis in intestinal organoids and find that dissipating this gradient by inhibiting Na-H exchanger 1 (NHE1) activity genetically or pharmacologically abolishes crypt budding. Using lineage tracing and single cell RNA sequencing we demonstrate that pHi dynamics acts downstream of Atoh1, with increased pHi promoting differentiation toward the secretory lineage, while reduced pHi biases differentiation into absorptive lineage. Consistent with this, disrupting the pHi gradient blocks new Paneth cell differentiation. Paneth cells provide an essential Wnt signal to ISCs in organoids, and we find that the loss of crypt budding upon NHE1 inhibition can be rescued with exogenous WNTs. Altogether, our findings indicate that pHi is tightly regulated in the ISC lineage and that an increase in pHi is required for Paneth cell specification and thus tissue maintenance. These observations reveal a previously unrecognized role for pHi dynamics in the cell fate specification within an adult stem cell lineage.

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Myogenic Progenitor Cell Lineage Specification by CRISPR/Cas9-based Transcriptional Activators

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