Epigenetic regulation of cell fate reprogramming in aging and disease: A predictive computational model

PLoS Computational Biology
Núria Folguera-BlascoTomás Alarcón


Understanding the control of epigenetic regulation is key to explain and modify the aging process. Because histone-modifying enzymes are sensitive to shifts in availability of cofactors (e.g. metabolites), cellular epigenetic states may be tied to changing conditions associated with cofactor variability. The aim of this study is to analyse the relationships between cofactor fluctuations, epigenetic landscapes, and cell state transitions. Using Approximate Bayesian Computation, we generate an ensemble of epigenetic regulation (ER) systems whose heterogeneity reflects variability in cofactor pools used by histone modifiers. The heterogeneity of epigenetic metabolites, which operates as regulator of the kinetic parameters promoting/preventing histone modifications, stochastically drives phenotypic variability. The ensemble of ER configurations reveals the occurrence of distinct epi-states within the ensemble. Whereas resilient states maintain large epigenetic barriers refractory to reprogramming cellular identity, plastic states lower these barriers, and increase the sensitivity to reprogramming. Moreover, fine-tuning of cofactor levels redirects plastic epigenetic states to re-enter epigenetic resilience, and vice versa. Our ense...Continue Reading


Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Apr 17, 2008·Molecular Systems Biology·Kim SneppenIan B Dodd
Jul 16, 2008·Current Opinion in Biotechnology·Bryan C DanielsChristopher R Myers
Sep 5, 2008·PloS One·Ben D MacArthurRichard O C Oreffo
Jan 29, 2009·Journal of Theoretical Biology·Diana David-RusAnirvan M Sengupta
Feb 11, 2009·Journal of the Royal Society, Interface·Tina ToniMichael P H Stumpf
Feb 4, 2010·Acta Neuropathologica·Fonnet E BleekerCornelis J F Van Noorden
Jan 1, 2006·Hereditary Cancer in Clinical Practice·Cjm LipsFl Moll
May 26, 2010·Journal of Clinical Pathology·Runjan Chetty
Aug 10, 2010·Trends in Molecular Medicine·Lenny DangShinsan M Su
Feb 16, 2011·Cell Research·Andrew J Bannister, Tony Kouzarides
Jul 26, 2011·Nature·Andrew AngelMartin Howard
Aug 27, 2011·BMC Medicine·Yuanyuan LiTrygve O Tollefsbol
Dec 20, 2011·Trends in Cell Biology·Shuo Han, Anne Brunet
Jul 10, 2012·Cell Metabolism·Chao Lu, Craig B Thompson
Aug 24, 2012·PLoS Computational Biology·Kim Sneppen, Ian B Dodd
Nov 20, 2012·Frontiers in Oncology·Jihye YunJason W Locasale
Mar 28, 2013·Current Neurology and Neuroscience Reports·Adam L CohenHoward Colman
May 28, 2013·Cancer Cell·Eric LetouzéJudith Favier
Jun 15, 2013·Cancer Cell·Ming Yang, Patrick J Pollard
Sep 4, 2013·The Journal of Clinical Investigation·Ming YangPatrick J Pollard
Oct 16, 2013·Cancer Letters·Christelle JohnsonJason W Locasale
Jan 18, 2014·Cancer Cell·Lindsay E WuDavid A Sinclair
Feb 15, 2014·Cell Cycle·Javier A MenendezJorge Joven
May 17, 2014·Neuro-oncology·Anne L BaldockKristin R Swanson
May 17, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Anne Brunet, Shelley L Berger
Aug 16, 2014·International Journal of Cancer. Journal International Du Cancer·Aurélie MorinJudith Favier
Oct 18, 2014·Frontiers in Oncology·Javier A Menendez, Tomás Alarcón
Nov 25, 2014·Cell·Brian K KennedyFelipe Sierra
Feb 14, 2015·Circulation Research·Samuel T Keating, Assam El-Osta
Feb 14, 2015·International Journal of Medical Sciences·Lilia DimitrovJohn D Heiss
Apr 14, 2015·The FEBS Journal·Stefan Nowicki, Eyal Gottlieb
Aug 25, 2015·The Journal of Chemical Physics·Roberto de la CruzTomás Alarcón
Sep 17, 2015·Nature Reviews. Molecular Cell Biology·Bérénice A BenayounAnne Brunet
Dec 3, 2015·Current Opinion in Chemical Biology·Xiaoyang SuJoshua D Rabinowitz
Dec 10, 2015·Annals of the New York Academy of Sciences·Samantha J Mentch, Jason W Locasale
Feb 16, 2016·Stem Cell Reports·Javier A MenendezTomás Alarcón
Feb 26, 2016·Science·Lacramioara BintuMichael B Elowitz
Mar 5, 2016·Nucleic Acids Research·Cecilia LövkvistJan O Haerter
Mar 5, 2016·Oncotarget·Javier A MenendezTomás Alarcón
Jun 4, 2016·Molecular Cell·Lauren N Booth, Anne Brunet
Jun 11, 2016·Trends in Biochemical Sciences·Shahaf PelegAxel Imhof
Jul 15, 2016·Physical Review. E·Kim Sneppen, Ian B Dodd
Jul 19, 2016·Trends in Molecular Medicine·Alejandro OcampoJuan Carlos Izpisua Belmonte
Aug 3, 2016·Science Advances·Sangita Pal, Jessica K Tyler
Aug 16, 2016·Cell·Payel SenShelley L Berger
Aug 20, 2016·Molecular Cell·Arnob DuttaJerry L Workman
Sep 14, 2016·Molecular Aspects of Medicine·Xia GaoJason W Locasale
Sep 17, 2016·Nature Reviews. Cancer·Adam KinnairdEvangelos D Michelakis
Dec 17, 2016·Cell·Alejandro OcampoJuan Carlos Izpisua Belmonte
Jan 4, 2017·Trends in Molecular Medicine·Peter L J de Keizer
Mar 9, 2017·Cell Metabolism·Upasna Sharma, Oliver J Rando
Mar 23, 2017·Scientific Reports·Llewellyn E JalbertSarah J Nelson
May 23, 2017·Frontiers in Cell and Developmental Biology·Javier A Menendez, Tomás Alarcón
Jul 22, 2017·Science·William A FlavahanBradley E Bernstein
Aug 16, 2017·Nature Cell Biology·Aimee FloresWilliam E Lowry


Jun 12, 2018·Cell Cycle·Elisabet CuyàsJavier A Menendez
May 1, 2019·PLoS Computational Biology·Núria Folguera-BlascoTomás Alarcón
Aug 25, 2019·Aging·Javier A MenendezTomás Alarcón
Apr 16, 2019·Frontiers in Plant Science·Maria Salomé Pais
Mar 14, 2021·Nature Communications·Sascha JungAntonio Del Sol

Methods Mentioned

histone acetylation

Related Concepts

Bayesian Prediction
Cell Differentiation Process
In Silico
Histone H7
Cell Aging
DNA Methylation

Related Feeds

Genetics & Epigenetics of Aging

Dozens of genes are implicated in lifespan, and epigenetic changes during aging affect cell function. This feed focuses on the genetics and epigenetics of aging.

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Aging-Associated Metabolic Disorders

Age is associated with many metabolic disorders including cardiovascular diseases, type 2 diabetes, stroke and heart disease. The mediators in aging process have been suggested to play a part in the cellular processes responsible for these metabolic disorders. Here is the latest research on aging-associated metabolic disorders.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Related Papers

Comparative and Functional Genomics
Lucia LatellaPier Lorenzo Puri
Nature Methods
Peter Karagiannis, Shinya Yamanaka
Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association
A Brotherton
© 2021 Meta ULC. All rights reserved