Metabolism as an early predictor of DPSCs aging

Dannie Macrin; Ammar Alghadeer; Yan Ting Zhao; Jason W. Miklas; Abdiasis M. Hussein; Damien Detraux; Aaron M. Robitaille; Anup Madan; Randall T. Moon; Yuliang Wang; Arikketh Devi; Julie Mathieu; Hannele Ruohola-Baker

doi:10.1038/s41598-018-37489-4

Metabolism as an early predictor of DPSCs aging

Dannie Macrin, Ammar Alghadeer, Yan Ting Zhao, Jason W. Miklas, Abdiasis M. Hussein, Damien Detraux, Aaron M. Robitaille, Anup Madan, Randall T. Moon, Yuliang Wang, Arikketh Devi, Julie Mathieu, Hannele Ruohola-Baker

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	2195
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-37489-4
Publication status	Published - 1 Dec 2019
Externally published	Yes

Funding

We thank the Ruohola-Baker lab, Dr. Ware and Dr. Davis for helpful discussion and Dr. Dodson, Dr. Popowics, Dr.Janebodin, UW dental clinic and patients who consented giving the extracted teeth for research purpose. We thank Luiza Carvalho, Ella Nestingen and Benjamin Baker for their help. This work is supported in part by the University of Washington\u2019s Proteomics Resource (UWPR95794). RTM is an Investigator of the HHMI. This work is supported in part by grants from CoMotion Innovation Fund, the National Institutes of Health R01GM097372, R01GM97372-03S1 and R01GM083867, 1P01GM081619 and the NHLBI Progenitor Cell Biology Consortium (U01HL099997; UO1HL099993) for HRB.

Funders	Funder number
H&R BLOCK
CoMotion Innovation Fund
National Institute of General Medical Sciences	R01GM097372, P01GM081619, R01GM083867
University of Washington	UWPR95794
National Institutes of Health	R01GM97372-03S1
National Institute of Diabetes and Digestive and Kidney Diseases	P30DK017047
National Heart, Lung, and Blood Institute	U01HL099997, U01HL099993
UK Research and Innovation	98052

Keywords

Adipogenesis
Biomarkers
Cell Differentiation
Cells, Cultured
Cellular Senescence
Dental Pulp/cytology
Energy Metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental
Humans
Immunophenotyping
Odontogenesis
Osteogenesis
Proteomics
Signal Transduction
Stem Cells/cytology
Transcriptome

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10.1038/s41598-018-37489-4

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@article{2a7ac2753f9249718a0eab05afe08d7a,

title = "Metabolism as an early predictor of DPSCs aging",

abstract = "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.",

keywords = "Adipogenesis, Biomarkers, Cell Differentiation, Cells, Cultured, Cellular Senescence, Dental Pulp/cytology, Energy Metabolism, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Immunophenotyping, Odontogenesis, Osteogenesis, Proteomics, Signal Transduction, Stem Cells/cytology, Transcriptome",

author = "Dannie Macrin and Ammar Alghadeer and Zhao, \{Yan Ting\} and Miklas, \{Jason W.\} and Hussein, \{Abdiasis M.\} and Damien Detraux and Robitaille, \{Aaron M.\} and Anup Madan and Moon, \{Randall T.\} and Yuliang Wang and Arikketh Devi and Julie Mathieu and Hannele Ruohola-Baker",

note = "Funding Information: We thank the Ruohola-Baker lab, Dr. Ware and Dr. Davis for helpful discussion and Dr. Dodson, Dr. Popowics, Dr.Janebodin, UW dental clinic and patients who consented giving the extracted teeth for research purpose. We thank Luiza Carvalho, Ella Nestingen and Benjamin Baker for their help. This work is supported in part by the University of Washington{\textquoteright}s Proteomics Resource (UWPR95794). RTM is an Investigator of the HHMI. This work is supported in part by grants from CoMotion Innovation Fund, the National Institutes of Health R01GM097372, R01GM97372-03S1 and R01GM083867, 1P01GM081619 and the NHLBI Progenitor Cell Biology Consortium (U01HL099997; UO1HL099993) for HRB. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-018-37489-4",

language = "English",

volume = "9",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - Metabolism as an early predictor of DPSCs aging

AU - Macrin, Dannie

AU - Alghadeer, Ammar

AU - Zhao, Yan Ting

AU - Miklas, Jason W.

AU - Hussein, Abdiasis M.

AU - Detraux, Damien

AU - Robitaille, Aaron M.

AU - Madan, Anup

AU - Moon, Randall T.

AU - Wang, Yuliang

AU - Devi, Arikketh

AU - Mathieu, Julie

AU - Ruohola-Baker, Hannele

N1 - Funding Information: We thank the Ruohola-Baker lab, Dr. Ware and Dr. Davis for helpful discussion and Dr. Dodson, Dr. Popowics, Dr.Janebodin, UW dental clinic and patients who consented giving the extracted teeth for research purpose. We thank Luiza Carvalho, Ella Nestingen and Benjamin Baker for their help. This work is supported in part by the University of Washington’s Proteomics Resource (UWPR95794). RTM is an Investigator of the HHMI. This work is supported in part by grants from CoMotion Innovation Fund, the National Institutes of Health R01GM097372, R01GM97372-03S1 and R01GM083867, 1P01GM081619 and the NHLBI Progenitor Cell Biology Consortium (U01HL099997; UO1HL099993) for HRB. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

KW - Adipogenesis

KW - Biomarkers

KW - Cell Differentiation

KW - Cells, Cultured

KW - Cellular Senescence

KW - Dental Pulp/cytology

KW - Energy Metabolism

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Developmental

KW - Humans

KW - Immunophenotyping

KW - Odontogenesis

KW - Osteogenesis

KW - Proteomics

KW - Signal Transduction

KW - Stem Cells/cytology

KW - Transcriptome

UR - https://www.scopus.com/pages/publications/85061754802

U2 - 10.1038/s41598-018-37489-4

DO - 10.1038/s41598-018-37489-4

M3 - Article

C2 - 30778087

AN - SCOPUS:85061754802

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 2195

ER -

Metabolism as an early predictor of DPSCs aging

Abstract

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Keywords

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