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Genome-wide maps of mRNAs and ncRNAs in aging and young dental pulp stem cells

ABSTRACT: Purpose: The goals of this study are to compare differentially expressed genes in young dental pulp stem cells to the aging dental pulp stem cells and to predict key regular factors. Methods: mRNA and ncRNA profiles of young and aging dental pulp stem cells were generated by deep sequencing, using BGISEQ-500 platform (BGI-Shenzhen, China). The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Agilent Technologies 2100 system and real-time quantitative PCR (QPCR) (TaqMan Probe). Results:After filtering out adaptor-related and low-quality sequences, 669 million clean reads in mRNA Library were generated. Clean reads was mapped to genome sequence with the mapping ratio from 88.54% to 97.61%. A total of 230487 mRNAs was obtained including 123724 known mRNAs and 106763 novel mRNAs respectively; In addition, we detected 177880 lncRNAs，139743 and 38137 were known and novel. For correlation analysis, the coefficient we obtained were all greater than 0.90, indicating a high biological correlation Conclusions: Our study represents the first detailed analysis of differentially expressed genes in aging and young dental pulp stem cells, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that hsa-miR-6724-5p may be a key node in the aging process of DPSCs, and its target genes was involved in the dopaminergic synapse

ORGANISM(S): Homo sapiens

PROVIDER: GSE185751 | GEO | 2021/11/28

REPOSITORIES: GEO

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Genome-wide maps of mRNAs and ncRNAs in aging and young dental pulp stem cells

Project description:Genome-wide maps of mRNAs and ncRNAs in aging and young dental pulp stem cells

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Gene expression profile during odontogenic differentiation was analyzed using a microarray (lncRNA).

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Project description:Tissue resident adult stem cells are known to participate in tissue regeneration and repair that follows cell turnover, or injury. It has been well established that aging impedes the regeneration capabilities at the cellular level, but it is not clear if the different onset of stem cell aging between individuals can be predicted or prevented at an earlier stage. Here we studied the dental pulp stem cells (DPSCs), a population of adult stem cells that is known to participate in the repair of an injured tooth, and its properties can be affected by aging. The dental pulp from third molars of a diverse patient group were surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteo/odontogenic and adipogenic lineages. Through RNA seq and qPCR analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput transcriptomic and proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-β) pathway and the cytoskeletal proteins are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs, prior to manifestation of senescence phenotypes. This metabolic signature therefore can be used to predict the onset of replicative senescence. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging.

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Project description:Pluripotent stem cells can switch their unique metabolic requirements to facilitate cellular changes but it is not clear if adult stem cells utilize metabolism in a similar manner. Here we studied the metabolism of a human adult stem cell: dental pulp stem cells (DPSCs). The dental pulp from third molars of a diverse patient group was surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteogenic and adipogenic lineages. Through RNA seq analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-β) pathway and the proteins associated with muscle contraction are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs. This metabolic signature can be used to predict the onset of replicative senescence phenotypes. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging.

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