A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Na Yang; James R. Occean; Daniël P. Melters; Changyou Shi; Lin Wang; Stephanie Stransky; Maire E. Doyle; Chang Yi Cui; Michael Delannoy; Jinshui Fan; Eliza Slama; Josephine M. Egan; Supriyo De; Steven C. Cunningham; Rafael de Cabo; Simone Sidoli; Yamini Dalal; Payel Sen

doi:10.1016/j.molcel.2023.04.005

A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Na Yang, James R. Occean, Daniël P. Melters, Changyou Shi, Lin Wang, Stephanie Stransky, Maire E. Doyle, Chang Yi Cui, Michael Delannoy, Jinshui Fan, Eliza Slama, Josephine M. Egan, Supriyo De, Steven C. Cunningham, Rafael de Cabo, Simone Sidoli, Yamini Dalal, Payel Sen

Biochemistry

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

4 Scopus citations

Abstract

Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcriptional suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.

Original language	English (US)
Pages (from-to)	1659-1676.e11
Journal	Molecular Cell
Volume	83
Issue number	10
DOIs	https://doi.org/10.1016/j.molcel.2023.04.005
State	Published - May 18 2023

Keywords

aging
chromatin
epigenetics
liver
regeneration

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2023.04.005

Cite this

Yang, N., Occean, J. R., Melters, D. P., Shi, C., Wang, L., Stransky, S., Doyle, M. E., Cui, C. Y., Delannoy, M., Fan, J., Slama, E., Egan, J. M., De, S., Cunningham, S. C., de Cabo, R., Sidoli, S., Dalal, Y., & Sen, P. (2023). A hyper-quiescent chromatin state formed during aging is reversed by regeneration. Molecular Cell, 83(10), 1659-1676.e11. https://doi.org/10.1016/j.molcel.2023.04.005

Yang, N, Occean, JR, Melters, DP, Shi, C, Wang, L, Stransky, S, Doyle, ME, Cui, CY, Delannoy, M, Fan, J, Slama, E, Egan, JM, De, S, Cunningham, SC, de Cabo, R, Sidoli, S, Dalal, Y & Sen, P 2023, 'A hyper-quiescent chromatin state formed during aging is reversed by regeneration', Molecular Cell, vol. 83, no. 10, pp. 1659-1676.e11. https://doi.org/10.1016/j.molcel.2023.04.005

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abstract = "Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcriptional suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.",

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author = "Na Yang and Occean, {James R.} and Melters, {Dani{\"e}l P.} and Changyou Shi and Lin Wang and Stephanie Stransky and Doyle, {Maire E.} and Cui, {Chang Yi} and Michael Delannoy and Jinshui Fan and Eliza Slama and Egan, {Josephine M.} and Supriyo De and Cunningham, {Steven C.} and {de Cabo}, Rafael and Simone Sidoli and Yamini Dalal and Payel Sen",

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doi = "10.1016/j.molcel.2023.04.005",

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AU - Occean, James R.

AU - Melters, Daniël P.

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AU - Stransky, Stephanie

AU - Doyle, Maire E.

AU - Cui, Chang Yi

AU - Delannoy, Michael

AU - Fan, Jinshui

AU - Slama, Eliza

AU - Egan, Josephine M.

AU - De, Supriyo

AU - Cunningham, Steven C.

AU - de Cabo, Rafael

AU - Sidoli, Simone

AU - Dalal, Yamini

AU - Sen, Payel

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AB - Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcriptional suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.

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KW - epigenetics

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KW - regeneration

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A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Abstract

Keywords

ASJC Scopus subject areas

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