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Human and murine transcriptome profiling identifies cross-species homology in pulmonary mononuclear phagocytes

ABSTRACT: Human and murine transcriptome profiling identifies cross-species homology in pulmonary mononuclear phagocytes

PROVIDER: PRJNA549448 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5208840.fastq.gz	Fastqsanger.gz
	SRR5208850.fastq.gz	Fastqsanger.gz
	SRR5208860.fastq.gz	Fastqsanger.gz
	SRR5208870.fastq.gz	Fastqsanger.gz
	SRR5208841.fastq.gz	Fastqsanger.gz

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Human and murine transcriptome profiling identifies cross-species homology in pulmonary mononuclear phagocytes [DCs and Monocytes]

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Human and murine transcriptome profiling identifies cross-species homology in pulmonary mononuclear phagocytes [DCs and Monocytes]

Project description:The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells. MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Though murine MPs are well characterized, their human homologues remain poorly understood, particularly in the lung and draining lymph nodes (LNs). Understanding these homologies, and their similarities and differences with murine MPs, is critical for identifying human genetic targets and thus developing human immunotherapies. To address this gap, we performed transcriptome-based alignment across fifteen distinct human and nine distinct murine lung and LN MPs. As controls to validate the analytical quality of cross-species pulmonary MP analysis, human blood and murine spleen MPs were used. Constrained canonical correlation, t-SNE and catplot visualization was used to align human and mouse MPs and identify MP subtypes with maximal correspondence across species. Among the top marker genes expressed in corresponding human-mouse MP pairs, only 30-10% of the genes overlapped, indicating a need for caution when identifying human gene variants and functions from mice. For instance, SPP1 is highly expressed in human interstitial macrophages but not alveolar macrophages (AMs), whereas in mice SSP1 is only expressed in AMs. Moreover, human LN dendritic cells (DCs) align best with murine LN DCs but not murine splenic DCs indicating cross-species similarity in tissue. Lastly, in both species, CD88 was the most useful cell surface marker for distinguishing monocyte/macrophages from DCs. Overall, these data provide a reference for analyzing cross-species transcriptome data and evaluating whether specific murine genes are suitable guides to identify the functionality of human MPs, or conversely, whether pursuing specific human genes in mice, is likely to be a valid and fruitful approach.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Human and Mouse Transcriptome Profiling Identifies Cross-Species Homology in Pulmonary and Lymph Node Mononuclear Phagocytes.

Project description:The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells (DCs). MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Although murine MPs are well characterized, their pulmonary and lymph node (LN) human homologs remain poorly understood. To address this gap, we have created a gene expression compendium across 24 distinct human and murine lung and LN MPs, along with human blood and murine spleen MPs, to serve as validation datasets. In-depth RNA sequencing identifies corresponding human-mouse MP subtypes and determines marker genes shared and divergent across species. Unexpectedly, only 13%-23% of the top 1,000 marker genes (i.e., genes not shared across species-specific MP subtypes) overlap in corresponding human-mouse MP counterparts. Lastly, CD88 in both species helps distinguish monocytes/macrophages from DCs. Our cross-species expression compendium serves as a resource for future translational studies to investigate beforehand whether pursuing specific MP subtypes or genes will prove fruitful.

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