Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice

Reyna Hernandez-Benitez; Chao Wang; Lei Shi; Yasuo Ouchi; Cuiqing Zhong; Tomoaki Hishida; Hsin Kai Liao; Eric A. Magill; Sebastian Memczak; Rupa D. Soligalla; Chiara Fresia; Fumiyuki Hatanaka; Veronica Lamas; Isabel Guillen; Sanjeeb Sahu; Mako Yamamoto; Yanjiao Shao; Alain Aguirre-Vazquez; Estrella Nuñez Delicado; Pedro Guillen; Concepcion Rodriguez Esteban; Jing Qu; Pradeep Reddy; Steve Horvath; Guang Hui Liu; Pierre Magistretti; Juan Carlos Izpisua Belmonte

doi:10.1016/j.xcrm.2024.101449

Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice

Reyna Hernandez-Benitez, Chao Wang, Lei Shi, Yasuo Ouchi, Cuiqing Zhong, Tomoaki Hishida, Hsin Kai Liao, Eric A. Magill, Sebastian Memczak, Rupa D. Soligalla, Chiara Fresia, Fumiyuki Hatanaka, Veronica Lamas, Isabel Guillen, Sanjeeb Sahu, Mako Yamamoto, Yanjiao Shao, Alain Aguirre-Vazquez, Estrella Nuñez Delicado, Pedro GuillenConcepcion Rodriguez Esteban, Jing Qu, Pradeep Reddy, Steve Horvath, Guang Hui Liu, Pierre Magistretti^*, Juan Carlos Izpisua Belmonte^*

^*Corresponding author for this work

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

7 Scopus citations

Abstract

Tissue regeneration following an injury requires dynamic cell-state transitions that allow for establishing the cell identities required for the restoration of tissue homeostasis and function. Here, we present a biochemical intervention that induces an intermediate cell state mirroring a transition identified during normal differentiation of myoblasts and other multipotent and pluripotent cells to mature cells. When applied in somatic differentiated cells, the intervention, composed of one-carbon metabolites, reduces some dedifferentiation markers without losing the lineage identity, thus inducing limited reprogramming into a more flexible cell state. Moreover, the intervention enabled accelerated repair after muscle injury in young and aged mice. Overall, our study uncovers a conserved biochemical transitional phase that enhances cellular plasticity in vivo and hints at potential and scalable biochemical interventions of use in regenerative medicine and rejuvenation interventions that may be more tractable than genetic ones.

Original language	English (US)
Article number	101449
Journal	Cell Reports Medicine
Volume	5
Issue number	3
DOIs	https://doi.org/10.1016/j.xcrm.2024.101449
State	Published - Mar 19 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

histone acetylation
myogenic lineage
one-carbon metabolism
regeneration
reprogramming
small molecules

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2024.101449

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Hernandez-Benitez, R., Wang, C., Shi, L., Ouchi, Y., Zhong, C., Hishida, T., Liao, H. K., Magill, E. A., Memczak, S., Soligalla, R. D., Fresia, C., Hatanaka, F., Lamas, V., Guillen, I., Sahu, S., Yamamoto, M., Shao, Y., Aguirre-Vazquez, A., Nuñez Delicado, E., ... Izpisua Belmonte, J. C. (2024). Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice. Cell Reports Medicine, 5(3), Article 101449. https://doi.org/10.1016/j.xcrm.2024.101449

@article{c04e88286cef45c9a04555d2d4ac8c24,

title = "Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice",

abstract = "Tissue regeneration following an injury requires dynamic cell-state transitions that allow for establishing the cell identities required for the restoration of tissue homeostasis and function. Here, we present a biochemical intervention that induces an intermediate cell state mirroring a transition identified during normal differentiation of myoblasts and other multipotent and pluripotent cells to mature cells. When applied in somatic differentiated cells, the intervention, composed of one-carbon metabolites, reduces some dedifferentiation markers without losing the lineage identity, thus inducing limited reprogramming into a more flexible cell state. Moreover, the intervention enabled accelerated repair after muscle injury in young and aged mice. Overall, our study uncovers a conserved biochemical transitional phase that enhances cellular plasticity in vivo and hints at potential and scalable biochemical interventions of use in regenerative medicine and rejuvenation interventions that may be more tractable than genetic ones.",

keywords = "histone acetylation, myogenic lineage, one-carbon metabolism, regeneration, reprogramming, small molecules",

author = "Reyna Hernandez-Benitez and Chao Wang and Lei Shi and Yasuo Ouchi and Cuiqing Zhong and Tomoaki Hishida and Liao, \{Hsin Kai\} and Magill, \{Eric A.\} and Sebastian Memczak and Soligalla, \{Rupa D.\} and Chiara Fresia and Fumiyuki Hatanaka and Veronica Lamas and Isabel Guillen and Sanjeeb Sahu and Mako Yamamoto and Yanjiao Shao and Alain Aguirre-Vazquez and \{Nu{\~n}ez Delicado\}, Estrella and Pedro Guillen and \{Rodriguez Esteban\}, Concepcion and Jing Qu and Pradeep Reddy and Steve Horvath and Liu, \{Guang Hui\} and Pierre Magistretti and \{Izpisua Belmonte\}, \{Juan Carlos\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = mar,

day = "19",

doi = "10.1016/j.xcrm.2024.101449",

language = "English (US)",

volume = "5",

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Hernandez-Benitez, R, Wang, C, Shi, L, Ouchi, Y, Zhong, C, Hishida, T, Liao, HK, Magill, EA, Memczak, S, Soligalla, RD, Fresia, C, Hatanaka, F, Lamas, V, Guillen, I, Sahu, S, Yamamoto, M, Shao, Y, Aguirre-Vazquez, A, Nuñez Delicado, E, Guillen, P, Rodriguez Esteban, C, Qu, J, Reddy, P, Horvath, S, Liu, GH, Magistretti, P & Izpisua Belmonte, JC 2024, 'Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice', Cell Reports Medicine, vol. 5, no. 3, 101449. https://doi.org/10.1016/j.xcrm.2024.101449

TY - JOUR

T1 - Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice

AU - Hernandez-Benitez, Reyna

AU - Wang, Chao

AU - Shi, Lei

AU - Ouchi, Yasuo

AU - Zhong, Cuiqing

AU - Hishida, Tomoaki

AU - Liao, Hsin Kai

AU - Magill, Eric A.

AU - Memczak, Sebastian

AU - Soligalla, Rupa D.

AU - Fresia, Chiara

AU - Hatanaka, Fumiyuki

AU - Lamas, Veronica

AU - Guillen, Isabel

AU - Sahu, Sanjeeb

AU - Yamamoto, Mako

AU - Shao, Yanjiao

AU - Aguirre-Vazquez, Alain

AU - Nuñez Delicado, Estrella

AU - Guillen, Pedro

AU - Rodriguez Esteban, Concepcion

AU - Qu, Jing

AU - Reddy, Pradeep

AU - Horvath, Steve

AU - Liu, Guang Hui

AU - Magistretti, Pierre

AU - Izpisua Belmonte, Juan Carlos

PY - 2024/3/19

Y1 - 2024/3/19

N2 - Tissue regeneration following an injury requires dynamic cell-state transitions that allow for establishing the cell identities required for the restoration of tissue homeostasis and function. Here, we present a biochemical intervention that induces an intermediate cell state mirroring a transition identified during normal differentiation of myoblasts and other multipotent and pluripotent cells to mature cells. When applied in somatic differentiated cells, the intervention, composed of one-carbon metabolites, reduces some dedifferentiation markers without losing the lineage identity, thus inducing limited reprogramming into a more flexible cell state. Moreover, the intervention enabled accelerated repair after muscle injury in young and aged mice. Overall, our study uncovers a conserved biochemical transitional phase that enhances cellular plasticity in vivo and hints at potential and scalable biochemical interventions of use in regenerative medicine and rejuvenation interventions that may be more tractable than genetic ones.

AB - Tissue regeneration following an injury requires dynamic cell-state transitions that allow for establishing the cell identities required for the restoration of tissue homeostasis and function. Here, we present a biochemical intervention that induces an intermediate cell state mirroring a transition identified during normal differentiation of myoblasts and other multipotent and pluripotent cells to mature cells. When applied in somatic differentiated cells, the intervention, composed of one-carbon metabolites, reduces some dedifferentiation markers without losing the lineage identity, thus inducing limited reprogramming into a more flexible cell state. Moreover, the intervention enabled accelerated repair after muscle injury in young and aged mice. Overall, our study uncovers a conserved biochemical transitional phase that enhances cellular plasticity in vivo and hints at potential and scalable biochemical interventions of use in regenerative medicine and rejuvenation interventions that may be more tractable than genetic ones.

KW - histone acetylation

KW - myogenic lineage

KW - one-carbon metabolism

KW - regeneration

KW - reprogramming

KW - small molecules

UR - http://www.scopus.com/inward/record.url?scp=85187977113&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2024.101449

DO - 10.1016/j.xcrm.2024.101449

M3 - Article

C2 - 38508141

AN - SCOPUS:85187977113

SN - 2666-3791

VL - 5

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 3

M1 - 101449

ER -

Intervention with metabolites emulating endogenous cell transitions accelerates muscle regeneration in young and aged mice

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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