Evidence map›Paper›PMID 39710699›Full record

ArticleSkeletal muscle2024

Mll4 in skeletal muscle fibers maintains muscle stem cells.

Yea-Eun Kim, Sang-Hyeon Hann, Young-Woo Jo, Kyusang Yoo, Ji-Hoon Kim, Jae W Lee, Young-Yun Kong

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Article in Skeletal muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yea-Eun KimSchool of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Sang-Hyeon HannSchool of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Young-Woo JoSchool of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Kyusang YooSchool of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Ji-Hoon KimMolecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
Jae W LeeDepartment of Biological Sciences, University at Buffalo, Buffalo, NY, 142604, USA.
Young-Yun KongSchool of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea. ykong@snu.ac.kr.

Funding

Transcription Factors Governing the Development of GHRH-neuronsR01NS118748 · NINDS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI LEE, JAE W, LEE, SOO-KYUNG · 2021 to 2024
$2.2M
National Research Foundation of Korea NRF-2022R1A2C3007621NINDS NIH HHS R01 NS118748
6 · The paper itself

Abstract

backgroundMuscle stem cells (MuSCs) undergo numerous state transitions throughout life, which are critical for supporting normal muscle growth and regeneration. Epigenetic modifications in skeletal muscle play a significant role in influencing the niche and cellular states of MuSCs. Mixed-lineage leukemia 4 (Mll4) is a histone methyltransferase critical for activating the transcription of various target genes and is highly expressed in skeletal muscle. This raises the question of whether Mll4 has a regulatory function in modulating the state transitions of MuSCs, warranting further investigation.

methodsTo assess if myofiber-expressed Mll4, a histone methyltransferase, contributes to the maintenance of MuSCs, we crossed MCK

resultsDuring postnatal myogenesis, Mll4 deleted muscles were observed with increased number of cycling MuSCs that proceeded to a differentiation state, leading to MuSC deprivation. This phenomenon occurred independently of gender. When Mll4 was ablated in adult muscles using the inducible method, adult MuSCs lost their quiescence and differentiated into myoblasts, also causing the depletion of MuSCs. Such roles of Mll4 in myofibers coincided with decreased expression levels of distinct Notch ligands: Jag1 and Dll1 in pubertal and Jag2 and Dll4 in adult muscles.

conclusionsOur study suggests that Mll4 is crucial for maintaining MuSCs in both pubertal and adult muscles, which may be accomplished through the modulation of distinct Notch ligand expressions in myofibers. These findings offer new insights into the role of myofiber-expressed Mll4 as a master regulator of MuSCs, highlighting its significance not only in developmental myogenesis but also in adult muscle, irrespective of sex.

Indexed as

Histone-Lysine N-MethyltransferaseMuscle Fibers, SkeletalAnimalsCalcium-Binding ProteinsCell DifferentiationFemaleMaleMiceMice, Inbred C57BLMice, KnockoutMuscle DevelopmentMuscle, SkeletalReceptors, NotchCalcium-Binding ProteinsDlk1 protein, mouseHistone-Lysine N-MethyltransferaseMLL4 protein, mouseReceptors, NotchExerciseMuscle stem cellsMyeloid/lymphoid or mixed-lineage leukemia 4 (Mll4)MyofiberNotch signalingSkeletal muscle

Identifiers

PMID39710699
PMCPMC11665228

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