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Gene expression across mammalian organ development.

ABSTRACT: The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.

SUBMITTER: Cardoso-Moreira M

PROVIDER: S-EPMC6658352 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Gene expression across mammalian organ development.

Cardoso-Moreira Margarida M Halbert Jean J Valloton Delphine D Velten Britta B Chen Chunyan C Shao Yi Y Liechti Angélica A Ascenção Kelly K Rummel Coralie C Ovchinnikova Svetlana S Mazin Pavel V PV Xenarios Ioannis I Harshman Keith K Mort Matthew M Cooper David N DN Sandi Carmen C Soares Michael J MJ Ferreira Paula G PG Afonso Sandra S Carneiro Miguel M Turner James M A JMA VandeBerg John L JL Fallahshahroudi Amir A Jensen Per P Behr Rüdiger R Lisgo Steven S Lindsay Susan S Khaitovich Philipp P Huber Wolfgang W Baker Julie J Anders Simon S Zhang Yong E YE Kaessmann Henrik H

Nature 20190626 7766

The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events ...[more]

PMID: 31243369

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Project description:BackgroundMicroarray expression profiling has been widely used to identify differentially expressed genes in complex cellular systems. However, while such methods can be used to directly infer intracellular regulation within homogeneous cell populations, interpretation of in vivo gene expression data derived from complex organs composed of multiple cell types is more problematic. Specifically, observed changes in gene expression may be due either to changes in gene regulation within a given cell type or to changes in the relative abundance of expressing cell types. Consequently, bona fide changes in intrinsic gene regulation may be either mimicked or masked by changes in the relative proportion of different cell types. To date, few analytical approaches have addressed this problem.ResultsWe have chosen to apply a computational method for deconvoluting gene expression profiles derived from intact tissues by using reference expression data for purified populations of the constituent cell types of the mammary gland. These data were used to estimate changes in the relative proportions of different cell types during murine mammary gland development and Ras-induced mammary tumorigenesis. These computational estimates of changing compartment sizes were then used to enrich lists of differentially expressed genes for transcripts that change as a function of intrinsic intracellular regulation rather than shifts in the relative abundance of expressing cell types. Using this approach, we have demonstrated that adjusting mammary gene expression profiles for changes in three principal compartments--epithelium, white adipose tissue, and brown adipose tissue--is sufficient both to reduce false-positive changes in gene expression due solely to changes in compartment sizes and to reduce false-negative changes by unmasking genuine alterations in gene expression that were otherwise obscured by changes in compartment sizes.ConclusionBy adjusting gene expression values for changes in the sizes of cell type-specific compartments, this computational deconvolution method has the potential to increase both the sensitivity and specificity of differential gene expression experiments performed on complex tissues. Given the necessity for understanding complex biological processes such as development and carcinogenesis within the context of intact tissues, this approach offers substantial utility and should be broadly applicable to identifying gene expression changes in tissues composed of multiple cell types.

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Gene expression across mammalian organ development.

Publications

Gene expression across mammalian organ development.

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