scholarly journals Single cell transcriptomics reveals a signaling roadmap coordinating endoderm and mesoderm diversification during foregut organogenesis

2019 ◽  
Author(s):  
Lu Han ◽  
Praneet Chaturvedi ◽  
Keishi Kishimoto ◽  
Hiroyuki Koike ◽  
Talia Nasr ◽  
...  

ABSTRACTVisceral organs, such as the lungs, stomach, liver and pancreas, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE) and the surrounding splanchnic mesoderm (SM). While patterning of DE lineages has been fairly well studied, paracrine signaling controlling SM regionalization and how this is coordinated with the epithelial identity during organogenesis is obscure. Here we used single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This uncovered an unexpected diversity in the SM cells that developed in close register with the organ-specific epithelium. From these data, we inferred a spatiotemporal signaling roadmap of the combinatorial endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validated key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging the signaling road map we generated different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive. The single cell data can be explored at: https://research.cchmc.org/ZornLab-singlecell.

2021 ◽  
Author(s):  
Jordan W. Squair ◽  
Michael A. Skinnider ◽  
Matthieu Gautier ◽  
Leonard J. Foster ◽  
Grégoire Courtine
Keyword(s):  

2021 ◽  
Vol 22 (S3) ◽  
Author(s):  
Yuanyuan Li ◽  
Ping Luo ◽  
Yi Lu ◽  
Fang-Xiang Wu

Abstract Background With the development of the technology of single-cell sequence, revealing homogeneity and heterogeneity between cells has become a new area of computational systems biology research. However, the clustering of cell types becomes more complex with the mutual penetration between different types of cells and the instability of gene expression. One way of overcoming this problem is to group similar, related single cells together by the means of various clustering analysis methods. Although some methods such as spectral clustering can do well in the identification of cell types, they only consider the similarities between cells and ignore the influence of dissimilarities on clustering results. This methodology may limit the performance of most of the conventional clustering algorithms for the identification of clusters, it needs to develop special methods for high-dimensional sparse categorical data. Results Inspired by the phenomenon that same type cells have similar gene expression patterns, but different types of cells evoke dissimilar gene expression patterns, we improve the existing spectral clustering method for clustering single-cell data that is based on both similarities and dissimilarities between cells. The method first measures the similarity/dissimilarity among cells, then constructs the incidence matrix by fusing similarity matrix with dissimilarity matrix, and, finally, uses the eigenvalues of the incidence matrix to perform dimensionality reduction and employs the K-means algorithm in the low dimensional space to achieve clustering. The proposed improved spectral clustering method is compared with the conventional spectral clustering method in recognizing cell types on several real single-cell RNA-seq datasets. Conclusions In summary, we show that adding intercellular dissimilarity can effectively improve accuracy and achieve robustness and that improved spectral clustering method outperforms the traditional spectral clustering method in grouping cells.


Cell ◽  
2021 ◽  
Author(s):  
Yuhan Hao ◽  
Stephanie Hao ◽  
Erica Andersen-Nissen ◽  
William M. Mauck ◽  
Shiwei Zheng ◽  
...  

Author(s):  
Zhen Miao ◽  
Benjamin D. Humphreys ◽  
Andrew P. McMahon ◽  
Junhyong Kim

2021 ◽  
pp. 338872
Author(s):  
Gerjen H. Tinnevelt ◽  
Kristiaan Wouters ◽  
Geert J. Postma ◽  
Rita Folcarelli ◽  
Jeroen J. Jansen

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A520-A520
Author(s):  
Son Pham ◽  
Tri Le ◽  
Tan Phan ◽  
Minh Pham ◽  
Huy Nguyen ◽  
...  

BackgroundSingle-cell sequencing technology has opened an unprecedented ability to interrogate cancer. It reveals significant insights into the intratumoral heterogeneity, metastasis, therapeutic resistance, which facilitates target discovery and validation in cancer treatment. With rapid advancements in throughput and strategies, a particular immuno-oncology study can produce multi-omics profiles for several thousands of individual cells. This overflow of single-cell data poses formidable challenges, including standardizing data formats across studies, performing reanalysis for individual datasets and meta-analysis.MethodsN/AResultsWe present BioTuring Browser, an interactive platform for accessing and reanalyzing published single-cell omics data. The platform is currently hosting a curated database of more than 10 million cells from 247 projects, covering more than 120 immune cell types and subtypes, and 15 different cancer types. All data are processed and annotated with standardized labels of cell types, diseases, therapeutic responses, etc. to be instantly accessed and explored in a uniform visualization and analytics interface. Based on this massive curated database, BioTuring Browser supports searching similar expression profiles, querying a target across datasets and automatic cell type annotation. The platform supports single-cell RNA-seq, CITE-seq and TCR-seq data. BioTuring Browser is now available for download at www.bioturing.com.ConclusionsN/A


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