Dataset Information

Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney.

ABSTRACT:

Background

Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics.

Results

We mapped transcriptomic signatures of scRNA-seq cell types upon the 9 and 18 PCW kidney sections based on cell-type deconvolution and multimodal intersection analyses, depicting a spatial landscape of developing cell subpopulations. We established the gene characteristics in the medullary regions and revealed a strong mitochondrial oxidative phosphorylation and glycolysis activity in the deeper medullary region. We also built a regulatory network centered on GDNF-ETV4 for nephrogenic niche development based on the weighted gene co-expression network analysis and highlighted the key roles of Wnt, FGF, and JAG1-Notch2 signaling in maintaining renal branching morphogenesis.

Conclusions

Our findings obtained by this spatiotemporal gene program are expected to improve the current understanding of kidney development.

SUBMITTER: Wu H

PROVIDER: S-EPMC9164720 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney.

Wu Hongwei H Liu Fanna F Shangguan Yu Y Yang Yane Y Shi Wei W Hu Wenlong W Zeng Zhipeng Z Hu Nan N Zhang Xinzhou X Hocher Berthold B Tang Donge D Yin Lianghong L Dai Yong Y

Cell & bioscience 20220603 1

<h4>Background</h4>Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics.<h4>Results</h4>We mapped transcriptomic signatures of scRNA-seq cell types upon the ...[more]

PMID: 35659756

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Project description:BackgroundThe transition of the myometrium from a quiescent to a contractile state during labour is known to involve inflammation, which is characterized by the infiltration of immune cells and the secretion of cytokines. However, the specific cellular mechanisms underlying inflammation in the myometrium during human parturition are not yet fully understood.MethodsThrough the analysis of transcriptomics, proteomics, and cytokine arrays, the inflammation in the human myometrium during labour was revealed. By performing single-cell RNA sequencing (scRNA-seq) and spatiotemporal transcriptomic (ST) analyses on human myometrium in term in labour (TIL) and term in non-labour (TNL), we established a comprehensive landscape of immune cells, their transcriptional characteristics, distribution, function and intercellular communications during labour. Histological staining, flow cytometry, and western blotting were applied to validate some results from scRNA-seq and ST.ResultsOur analysis identified immune cell types, including monocytes, neutrophils, T cells, natural killer (NK) cells and B cells, present in the myometrium. TIL myometrium had a higher proportion of monocytes and neutrophils than TNL myometrium. Furthermore, the scRNA-seq analysis showed an increase in M1 macrophages in TIL myometrium. CXCL8 expression was mainly observed in neutrophils and increased in TIL myometrium. CCL3 and CCL4 were principally expressed in M2 macrophages and neutrophils-6, and decreased during labour; XCL1 and XCL2 were specifically expressed in NK cells, and decreased during labour. Analysis of cytokine receptor expression revealed an increase in IL1R2, which primarily expressed in neutrophils. Finally, we visualized the spatial proximity of representative cytokines, contraction-associated genes, and corresponding receptors in ST to demonstrate their location within the myometrium.ConclusionsOur analysis comprehensively revealed changes in immune cells, cytokines, and cytokine receptors during labour. It provided a valuable resource to detect and characterize inflammatory changes, yielding insights into the immune mechanisms underlying labour.

Dataset Information

Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney.

Background

Results

Conclusions

Publications

Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney.

Similar Datasets

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