Understanding the regulatory networks that control adult stem cell homeostasis during aging is a critical step in discovering ways to preserve the function of different tissues throughout lifespan. Ultra-high-Throughput sequencing approaches will allow the unbiased genome-wide identification of transcriptional regulator binding sites and histone modification patterns in aging stem cells. This knowledge will be pivotal to decipher the molecular mechanisms that maintain stem cell reservoirs in adult organisms. The mission of the Genomics and Ultra-High-Throughput Sequencing Core will be: 1. To generate consistent data for transcription factor binding sites, epigenetic modifications on chromatin, and RNA transcripts that can be shared between the three laboratories of the Program Project; 2. To provide computational and statistical support for data analysis and to develop new bioinformatic approaches for the combined analysis of datasets from different stem cell types at different ages; 3. To establish and maintain a data management system that will facilitate data exchange between the participating laboratories.

Public Health Relevance

The unbiased identification of age-dependent changes in transcriptional and epigenetic networks in adult stem cells will be pivotal for determining the mechanisms underlying the regulation of these cells throughout life, and will help uncover new avenues to counteract age-dependent decline in tissue regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG036695-03
Application #
8495859
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$165,485
Indirect Cost
$79,862
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
de Morrée, Antoine; van Velthoven, Cindy T J; Gan, Qiang et al. (2017) Staufen1 inhibits MyoD translation to actively maintain muscle stem cell quiescence. Proc Natl Acad Sci U S A 114:E8996-E9005
Rando, Thomas A (2017) Fleeting factors, turning back time. Nat Biotechnol 35:218-220
van Velthoven, Cindy T J; de Morree, Antoine; Egner, Ingrid M et al. (2017) Transcriptional Profiling of Quiescent Muscle Stem Cells In Vivo. Cell Rep 21:1994-2004
Dulken, Ben W; Leeman, Dena S; Boutet, Stéphane C et al. (2017) Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage. Cell Rep 18:777-790
Rodgers, Joseph T; Schroeder, Matthew D; Ma, Chanthia et al. (2017) HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem Cells into GAlert. Cell Rep 19:479-486
Stearns-Reider, Kristen M; D'Amore, Antonio; Beezhold, Kevin et al. (2017) Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion. Aging Cell 16:518-528
Quarta, Marco; Cromie, Melinda; Chacon, Robert et al. (2017) Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss. Nat Commun 8:15613
Brunet, Anne; Rando, Thomas A (2017) Interaction between epigenetic and metabolism in aging stem cells. Curr Opin Cell Biol 45:1-7
Luo, Dan; de Morree, Antoine; Boutet, Stephane et al. (2017) Deltex2 represses MyoD expression and inhibits myogenic differentiation by acting as a negative regulator of Jmjd1c. Proc Natl Acad Sci U S A 114:E3071-E3080
Du, Hongqing; Shih, Chung-Hsuan; Wosczyna, Michael N et al. (2017) Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nat Commun 8:669

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