TY - JOUR
T1 - Tissue, age, sex, and disease patterns of matrisome expression in GTEx transcriptome data
AU - Nieuwenhuis, Tim O.
AU - Rosenberg, Avi Z.
AU - McCall, Matthew N.
AU - Halushka, Marc K.
N1 - Funding Information:
This work was supported by the National Institutes of Health Grants 1R01HL137811 (MKH), R01GM130564 (MKH), R01GM139928 (MNM), and the University of Rochester CTSA award number UL1TR002001 (MNM). We would like to thank Dan Arking for his helpful comments on the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally matched proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 382 gene transcripts varied by age and 315 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized matrix control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis (IPF) matrix changes, while identifying 22 matrix genes upregulated in IPF. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.
AB - The extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally matched proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 382 gene transcripts varied by age and 315 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized matrix control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis (IPF) matrix changes, while identifying 22 matrix genes upregulated in IPF. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.
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U2 - 10.1038/s41598-021-00943-x
DO - 10.1038/s41598-021-00943-x
M3 - Article
C2 - 34732773
AN - SCOPUS:85118495764
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 21549
ER -