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Using toponomics to characterize phenotypic diversity in alveolar macrophages from male mice treated with exogenous SP-A1.

ABSTRACT: Background:We used the Toponome Imaging System (TIS) to identify "patterns of marker expression", referred to here as combinatorial molecular phenotypes (CMPs) in alveolar macrophages (AM) in response to the innate immune molecule, SP-A1. Methods:We compared 114?AM from male SP-A deficient mice. One group (n?=?3) was treated with exogenous human surfactant protein A1 (hSP-A1) and the other with vehicle (n?=?3). AM obtained by bronchoalveolar lavage were plated onto slides and analyzed using TIS to study the AM toponome, the spatial network of proteins within intact cells. With TIS, each slide is sequentially immunostained with multiple FITC-conjugated antibodies. Images are analyzed pixel-by-pixel identifying all of the proteins within each pixel, which are then designated as CMPs. CMPs represent organized protein clusters postulated to contribute to specific functions. Results:1) We compared identical CMPs in KO and SP-A1 cells and found them to differ significantly (p?=?0.0007). Similarities between pairs of markers in the two populations also differed significantly (p?

SUBMITTER: Phelps DS

PROVIDER: S-EPMC7020580 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Using toponomics to characterize phenotypic diversity in alveolar macrophages from male mice treated with exogenous SP-A1.

Phelps David S DS Chinchilli Vernon M VM Weisz Judith J Shearer Debra D Zhang Xuesheng X Floros Joanna J

Biomarker research 20200213

<h4>Background</h4>We used the Toponome Imaging System (TIS) to identify "patterns of marker expression", referred to here as combinatorial molecular phenotypes (CMPs) in alveolar macrophages (AM) in response to the innate immune molecule, SP-A1.<h4>Methods</h4>We compared 114 AM from male SP-A deficient mice. One group (<i>n</i> = 3) was treated with exogenous human surfactant protein A1 (hSP-A1) and the other with vehicle (<i>n</i> = 3). AM obtained by bronchoalveolar lavage were plated onto s ...[more]

PMID: 32082572

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Project description:BackgroundAnalyzing and understanding the relationship between genotypes and phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis elegans has been instrumental for unraveling genotype-phenotype relations, and has important implications for understanding the biology of mammals, but almost all studies, including forward and reverse genetic screens, are limited by investigations in only one canonical genotype. This hampers the detection and functional analysis of allelic variants, which play a key role in controlling many complex traits. It is therefore essential to explore the full potential of the natural genetic variation and evolutionary context of the genotype-phenotype map in wild C. elegans populations.ResultsWe used multiple wild C. elegans populations freshly isolated from local sites to investigate gene sequence polymorphisms and a multitude of phenotypes including the transcriptome, fitness, and behavioral traits. The genotype, transcriptome, and a number of fitness traits showed a direct link with the original site of the strains. The separation between the isolation sites was prevalent on all chromosomes, but chromosome V was the largest contributor to this variation. These results were supported by a differential food preference of the wild isolates for naturally co-existing bacterial species. Comparing polymorphic genes between the populations with a set of genes extracted from 19 different studies on gene expression in C. elegans exposed to biotic and abiotic factors, such as bacteria, osmotic pressure, and temperature, revealed a significant enrichment for genes involved in gene-environment interactions and protein degradation.ConclusionsWe found that wild C. elegans populations are characterized by gene-environment signatures, and we have unlocked a wealth of genotype-phenotype relations for the first time. Studying natural isolates provides a treasure trove of evidence compared with that unearthed by the current research in C. elegans, which covers only a diminutive part of the myriad of genotype-phenotype relations that are present in the wild.

Dataset Information

Using toponomics to characterize phenotypic diversity in alveolar macrophages from male mice treated with exogenous SP-A1.

Publications

Using toponomics to characterize phenotypic diversity in alveolar macrophages from male mice treated with exogenous SP-A1.

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