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. 2024 Sep 1;79(9):glae147.
doi: 10.1093/gerona/glae147.

Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations

Jack Feehan  1   2 , Nicholas Tripodi  2   3 , Dmitry Kondrikov  4 , Tissa Wijeratne  1   3 , Jeffrey Gimble  5 , William Hill  6   7 , Vasso Apostolopoulos  2   3 , Gustavo Duque  8   9
Affiliations

Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations

Jack Feehan et al. J Gerontol A Biol Sci Med Sci. .

Abstract

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in 3 different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from men and women. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype in the analysis of pooled older stem cells, suggestive of suppressed proliferation and differentiation; however, these changes were not reflected in the proteome of the cells. Analyzed independently, older MPCs had a distinct phenotype in both the transcriptome and proteome consistent with altered differentiation and proliferation with a proinflammatory immune shift in older adults. COP cells showed a transcriptomic shift to proinflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shifts in physiologies associated with cell migration, adherence, and immune activation but no proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that may contribute to a decline in tissue regeneration. However, the proteome of the cells was inconsistently regulated.

Keywords: Adipose-derived stem cells; Circulating osteoprogenitors; Geroscience; Mesenchymal stem cells; Stem cells.

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Conflict of interest statement

None.

Figures

Figure 1.
Figure 1.
Differential expression of genes across cells grouped by age. (A) PCA plot showing clustering by cell type, rather than age, (B) Volcano plot showing differential expression of younger samples, compared to older, (C) Biological process enrichment analysis, (D) Heatmap showing differentially expressed genes. ADASC = Adipose-derived adult stem cells; COP = Circulating osteoprogenitor cells; OM = Older Male; OF: Older Female; MPC = Mesenchymal stem and progenitor cells; YM = Young Male; YF: Young Female.
Figure 2.
Figure 2.
Circular network plot showing the differentially regulated genes and their biological process ontologies.
Figure 3.
Figure 3.
Transcriptome analysis of MPCs. (A) PCA plot showing limited clustering of samples by age, (B) Volcano plot showing differentially expressed genes in younger donors versus older, (C) Biological process ontology enrichment analysis of differentially expressed genes, and (D) Clustered heat map showing differentially expressed genes across the data set. ADASC = Adipose-derived adult stem cells; COP = Circulating osteoprogenitor cells; MPC = Mesenchymal stem and progenitor cells; OM = Older Male; OF = Older Female; YM = Young Male; YF = Young Female.
Figure 4.
Figure 4.
Proteomic analysis of MPCs (A) Heatmap showing differentially expressed proteins between older and younger donors, (B) Volcano plot showing differentially expressed proteins between younger and older, (C) Biological process ontology analysis showing enrichment of pathways in the set, (D) Circular network plot showing proteins and their associations with the enriched pathways. ADASC = Adipose-derived adult stem cells; COP = Circulating osteoprogenitor cells; MPC = Mesenchymal stem and progenitor cells; OM = Older Male; OF = Older Female; YM = Young Male; YF = Young Female.
Figure 5.
Figure 5.
Differential expression of genes across COP cells grouped by age. (A) PCA plot showing limited clustering by age, (B) Volcano plot showing differential expression of younger samples, compared to older, (C) Biological process enrichment analysis, (D) Heatmap showing differentially expressed genes. ADASC = Adipose-derived adult stem cells; COP = Circulating osteoprogenitor cells; MPC = Mesenchymal stem and progenitor cells; OM = Older Male; OF = Older Female; YM = Young Male; YF = Young Female.
Figure 6.
Figure 6.
Differential expression of genes across ADSCs grouped by age. (A) PCA plot showing no clustering by age, (B) Volcano plot showing differential expression of younger samples, compared to older, (C) Biological process enrichment analysis, (D) Heatmap showing differentially expressed genes. ADASC = Adipose-derived adult stem cells; COP = Circulating osteoprogenitor cells; MPC = Mesenchymal stem and progenitor cells; OM = Older Male; OF = Older Female; YM = Young Male; YF = Young Female.
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