Gene Expression and Cell-Cell Interactions in the Developing Nervous System

1984 ◽  
Author(s):  
Erick Armingol ◽  
Adam Officer ◽  
Olivier Harismendy ◽  
Nathan E. Lewis

1997 ◽  
Vol 3 (4) ◽  
pp. 290-298 ◽  
Author(s):  
Fabrizio Ensoli ◽  
Hong Wang ◽  
Valeria Fiorelli ◽  
Steven L Zeichner ◽  
Maria Rita De Cristofaro ◽  
...  

2021 ◽  
Author(s):  
Brendan T Innes ◽  
Gary D Bader

Cell-cell interactions are often predicted from single-cell transcriptomics data based on observing receptor and corresponding ligand transcripts in cells. These predictions could theoretically be improved by inspecting the transcriptome of the receptor cell for evidence of gene expression changes in response to the ligand. It is commonly expected that a given receptor, in response to ligand activation, will have a characteristic downstream gene expression signature. However, this assumption has not been well tested. We used ligand perturbation data from both the high-throughput Connectivity Map resource and published transcriptomic assays of cell lines and purified cell populations to determine whether ligand signals have unique and generalizable transcriptional signatures across biological conditions. Most of the receptors we analyzed did not have such characteristic gene expression signatures - instead these signatures were highly dependent on cell type. Cell context is thus important when considering transcriptomic evidence of ligand signaling, which makes it challenging to build generalizable ligand-receptor interaction signatures to improve cell-cell interaction predictions.


Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 953-966 ◽  
Author(s):  
R.L. Bennett ◽  
F.M. Hoffmann

Mutations in the Drosophila Abelson tyrosine kinase have pleiotropic effects late in development that lead to pupal lethality or adults with a reduced life span, reduced fecundity and rough eyes. We have examined the expression of the abl protein throughout embryonic and pupal development and analyzed mutant phenotypes in some of the tissues expressing abl. abl protein, present in all cells of the early embryo as the product of maternally contributed mRNA, transiently localizes to the region below the plasma membrane cleavage furrows as cellularization initiates. The function of this expression is not yet known. Zygotic expression of abl is first detected in the post-mitotic cells of the developing muscles and nervous system midway through embryogenesis. In later larval and pupal stages, abl protein levels are also highest in differentiating muscle and neural tissue including the photoreceptor cells of the eye. abl protein is localized subcellularly to the axons of the central nervous system, the embryonic somatic muscle attachment sites and the apical cell junctions of the imaginal disk epithelium. Evidence for abl function was obtained by analysis of mutant phenotypes in the embryonic somatic muscles and the eye imaginal disk. The expression patterns and mutant phenotypes indicate a role for abl in establishing and maintaining cell-cell interactions.


Cell Systems ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 496-507.e6 ◽  
Author(s):  
Simon van Vliet ◽  
Alma Dal Co ◽  
Annina R. Winkler ◽  
Stefanie Spriewald ◽  
Bärbel Stecher ◽  
...  

1987 ◽  
Vol 12 (11) ◽  
pp. 1005-1012
Author(s):  
Donna M. Bozzone ◽  
Russel E. Kohnken ◽  
Edward A. Berger

2021 ◽  
Author(s):  
Bianca C.T Flores ◽  
Smriti Chawla ◽  
Ning Ma ◽  
Chad Sanada ◽  
Praveen Kumar Kujur ◽  
...  

Cell-cell communication and physical interactions play a vital role in cancer initiation, homeostasis, progression, and immune response. Here, we report a system that combines live capture of different cell types, co-incubation, time-lapse imaging, and gene expression profiling of doublets using a microfluidic integrated fluidic circuit (IFC) that enables measurement of physical distances between cells and the associated transcriptional profiles due to cell-cell interactions. The temporal variations in natural killer (NK) - triple-negative breast cancer (TNBC) cell distances were tracked and compared with terminally profiled cellular transcriptomes. The results showed the time-bound activities of regulatory modules and alluded to the existence of transcriptional memory. Our experimental and bioinformatic approaches serve as a proof of concept for interrogating live cell interactions at doublet resolution, which can be applied across different cancers and cell types.


2021 ◽  
Author(s):  
Kun Wang ◽  
Sushant Patkar ◽  
Joo Sang Lee ◽  
E. Michael Gertz ◽  
Welles Robinson ◽  
...  

AbstractThe tumor microenvironment (TME) is a complex mixture of cell-types that interact with each other to affect tumor growth and clinical outcomes. To accelerate the discovery of such interactions, we developed CODEFACS (COnfident DEconvolution For All Cell Subsets), a deconvolution tool inferring cell-type-specific gene expression in each sample from bulk expression measurements, and LIRICS (LIgand Receptor Interactions between Cell Subsets), a supporting pipeline that analyzes the deconvolved gene expression from CODEFACS to identify clinically relevant ligand-receptor interactions between cell-types. Using 15 benchmark test datasets, we first demonstrate that CODEFACS substantially improves the ability to reconstruct cell-type-specific transcriptomes from individual bulk samples, compared to the state-of-the-art method, CIBERSORTx. Second, analyzing the TCGA, we uncover cell-cell interactions that specifically occur in TME of mismatch-repair-deficient tumors and are associated with their high response rates to anti-PD1 treatment. These results point to specific T-cell co-stimulating interactions that enhance immunotherapy responses in tumors independently of their mutation burden levels. Finally, using machine learning, we identify a subset of cell-cell interactions that predict patient response to anti-PD1 therapy in melanoma better than recently published bulk transcriptomics-based signatures. CODEFACS offers a way to study bulk cancer and normal transcriptomes at a cell type-specific resolution, complementing single-cell transcriptomics.


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