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Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

Lissner MM, Thomas BJ, Wee K, Tong AJ, Kollmann TR, Smale ST - PLoS ONE (2015)

Bottom Line: A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults.By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults.Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.

ABSTRACT
A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.

No MeSH data available.


Related in: MedlinePlus

Analysis of LPS-induced genes in monocytes by K-means cluster analysis.(A) The 1147 genes that exceeded 200 bp in length, exhibited an RPKM of at least 4 in one sample, and were induced by LPS by at least 5-fold in the same sample were divided into 10 clusters by k-means cluster analysis, which considers similarities in transcript levels for each gene across all 27 samples (3 age groups, 3 samples for each age group, and 3 time points for each sample). The three independent samples are shown in parallel for each age group. Colors indicate the percentile of the relative expression level (based on the log-transformed mean-centered RPKM for each gene), as indicated at the bottom. (B) The average relative transcript levels for genes within each cluster are shown for each age group (neonates, blue diamonds; young adults, red squares; older adults, green triangles).
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pone.0132061.g003: Analysis of LPS-induced genes in monocytes by K-means cluster analysis.(A) The 1147 genes that exceeded 200 bp in length, exhibited an RPKM of at least 4 in one sample, and were induced by LPS by at least 5-fold in the same sample were divided into 10 clusters by k-means cluster analysis, which considers similarities in transcript levels for each gene across all 27 samples (3 age groups, 3 samples for each age group, and 3 time points for each sample). The three independent samples are shown in parallel for each age group. Colors indicate the percentile of the relative expression level (based on the log-transformed mean-centered RPKM for each gene), as indicated at the bottom. (B) The average relative transcript levels for genes within each cluster are shown for each age group (neonates, blue diamonds; young adults, red squares; older adults, green triangles).

Mentions: To extend the analysis of age-related differences in inducible gene expression, k-means clustering was used to define groups of genes that exhibited similar expression patterns among the three age groups and three time points. The k-means algorithm considers induction kinetics, induction magnitudes, and differences among age groups. Fig 3A shows the results obtained when the 1147 LPS-induced genes (using the average expression values from the three independent samples analyzed for each age group and each time point) were assigned to one of ten distinct clusters. As expected on the basis of the hierarchical clustering, extensive similarities were apparent in the three age groups in almost all of the clusters. The similarities are also apparent in line graphs showing the average relative expression levels for all genes in a given cluster (Fig 3B).


Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

Lissner MM, Thomas BJ, Wee K, Tong AJ, Kollmann TR, Smale ST - PLoS ONE (2015)

Analysis of LPS-induced genes in monocytes by K-means cluster analysis.(A) The 1147 genes that exceeded 200 bp in length, exhibited an RPKM of at least 4 in one sample, and were induced by LPS by at least 5-fold in the same sample were divided into 10 clusters by k-means cluster analysis, which considers similarities in transcript levels for each gene across all 27 samples (3 age groups, 3 samples for each age group, and 3 time points for each sample). The three independent samples are shown in parallel for each age group. Colors indicate the percentile of the relative expression level (based on the log-transformed mean-centered RPKM for each gene), as indicated at the bottom. (B) The average relative transcript levels for genes within each cluster are shown for each age group (neonates, blue diamonds; young adults, red squares; older adults, green triangles).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493075&req=5

pone.0132061.g003: Analysis of LPS-induced genes in monocytes by K-means cluster analysis.(A) The 1147 genes that exceeded 200 bp in length, exhibited an RPKM of at least 4 in one sample, and were induced by LPS by at least 5-fold in the same sample were divided into 10 clusters by k-means cluster analysis, which considers similarities in transcript levels for each gene across all 27 samples (3 age groups, 3 samples for each age group, and 3 time points for each sample). The three independent samples are shown in parallel for each age group. Colors indicate the percentile of the relative expression level (based on the log-transformed mean-centered RPKM for each gene), as indicated at the bottom. (B) The average relative transcript levels for genes within each cluster are shown for each age group (neonates, blue diamonds; young adults, red squares; older adults, green triangles).
Mentions: To extend the analysis of age-related differences in inducible gene expression, k-means clustering was used to define groups of genes that exhibited similar expression patterns among the three age groups and three time points. The k-means algorithm considers induction kinetics, induction magnitudes, and differences among age groups. Fig 3A shows the results obtained when the 1147 LPS-induced genes (using the average expression values from the three independent samples analyzed for each age group and each time point) were assigned to one of ten distinct clusters. As expected on the basis of the hierarchical clustering, extensive similarities were apparent in the three age groups in almost all of the clusters. The similarities are also apparent in line graphs showing the average relative expression levels for all genes in a given cluster (Fig 3B).

Bottom Line: A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults.By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults.Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.

ABSTRACT
A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.

No MeSH data available.


Related in: MedlinePlus