FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age

García‐Prat, Laura; Perdiguero, Eusebio; Alonso-Martín, Sonia; Dell’Orso, Stefania; Ravichandran, Srikanth; Brooks, Stephen R.; Juan, Aster H.; Campanario, Silvia; Jiang, Kan; Hong, Xiaotong; Ortet, Laura; Ruiz‐Bonilla, Vanessa; Flández, Marta; Moiseeva, Victoria; Rebollo, Elena; Jardı́, Mercè; Sun, Hongwei; Musarò, Antonio; Sandri, Marco; Sol, Antonio del; Sartorelli, Vittorio; Muñoz‐Cánoves, Pura

doi:10.1038/s41556-020-00593-7

Cited by 122 publications

(101 citation statements)

References 63 publications

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“…Age-dependent transcriptome changes of MuSCs have been characterized in multiple studies; however, transcript levels can only partially predict changes at the protein level during aging due to a progressive decoupling between the transcriptome and proteome during aging (Janssens et al, 2015;Kelmer Sacramento et al, 2020;Ori et al, 2015;Wei et al, 2015). To investigate if the proteome and transcriptome are also uncoupled in aging MuSC, we re-analyzed transcriptome data from three independent studies based on microarray technology (Alonso-Martin et al, 2016;Liu et al, 2013;Lukjanenko et al, 2016;Price et al, 2014) and two recent datasets obtained by RNA sequencing (RNA-seq; García-Prat et al, 2020;Li et al, 2019). We compared age-related transcriptome and proteome changes by focusing on the 162 proteins significantly affected in both old and geriatric MuSCs (Figure 1E).…”

Section: Aging Changes the Proteome Of Muscsmentioning

confidence: 99%

Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality

et al. 2021

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Section: Aging Changes the Proteome Of Muscsmentioning

confidence: 99%

Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality

et al. 2021

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“…MuSC quiescent state is characterized by the expression of PAX7 and FOXO transcription factors [13]. Myf5 and Myod1 are also transcribed in quiescent MuSCs, but post-transcriptional regulation prevents their translation (PAX7 + FOXO + MYF5 -MYOD1 -) ( Fig.…”

Section: Muscs Mediate Regeneration Of Skeletal Musclementioning

confidence: 99%

“…Myf5 and Myod1 are also transcribed in quiescent MuSCs, but post-transcriptional regulation prevents their translation (PAX7 + FOXO + MYF5 -MYOD1 -) ( Fig. 1) [13,14]. More specifically, Myf5 mRNA is sequestered in messenger ribonucleoprotein granules (mRNPs) to avoid its translation [15] while Myod1 mRNA retains an intron that prevents its translocation out of the nucleus [16].…”

Section: Muscs Mediate Regeneration Of Skeletal Musclementioning

confidence: 99%

“…As the MuSCs start to accumulate, PAX7 and MYF5 expression becomes repressed while MYOG becomes expressed to drive cell cycle exit and form myocytes (PAX7 --FOXO -MYF5 -MYOD1 + MYOG + ) ( Fig. 1) [13,18]. Finally, the formation of multinucleated myofibers results in the decreased expression of MYOD1 while MYF6/MRF4 becomes highly expressed in the functional muscle fiber [19][20][21].…”

Section: Muscs Mediate Regeneration Of Skeletal Musclementioning

confidence: 99%

“…To maintain this balance, different pathways contribute to the quiescent MuSC transcriptional network. In particular, the expression of forkhead box (FOXO) transcription factors, FOXO1, FOXO3A, and FOXO4, were reported to be required for the maintenance of the MuSC quiescence [13]. FOXO3 maintains the expression of Notch pathway components [27].…”

Section: Quiescence and Early Activationmentioning

confidence: 99%

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Epigenetic regulation of satellite cell fate during skeletal muscle regeneration

et al. 2021

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In response to muscle injury, muscle stem cells integrate environmental cues in the damaged tissue to mediate regeneration. These environmental cues are tightly regulated to ensure expansion of muscle stem cell population to repair the damaged myofibers while allowing repopulation of the stem cell niche. These changes in muscle stem cell fate result from changes in gene expression that occur in response to cell signaling from the muscle environment.Integration of signals from the muscle environment leads to changes in gene expression through epigenetic mechanisms. Such mechanisms, including post-translational modification of chromatin and nucleosome repositioning, act to make specific gene loci more, or less, accessible to the transcriptional machinery. In youth, the muscle environment is ideally structured to allow for coordinated signaling that mediates efficient regeneration. Both age and disease alter the muscle environment such that the signaling pathways that shape the healthy muscle stem cell epigenome are altered. Altered epigenome reduces the efficiency of cell fate transitions required for muscle repair and contributes to muscle pathology. However, the reversible nature of epigenetic changes holds out potential for restoring cell fate potential to improve muscle repair in myopathies.In this review, we will describe the current knowledge of the mechanisms allowing muscle stem cell fate transitions during regeneration and how it is altered in muscle disease. In addition, we provide some examples of how epigenetics could be harnessed therapeutically to improve regeneration in various muscle pathologies.

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FoxO1 signaling in B cell malignancies and its therapeutic targeting

Hlavac,

Pavelkova,

Ondrisova

et al. 2024

FEBS Letters

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FoxO transcription factors (FoxO1, FoxO3a, FoxO4, FoxO6) are a highly evolutionary conserved subfamily of the ‘forkhead’ box proteins. They have traditionally been considered tumor suppressors, but FoxO1 also exhibits oncogenic properties. The complex nature of FoxO1 is illustrated by its various roles in B cell development and differentiation, immunoglobulin gene rearrangement and cell‐surface B cell receptor (BCR) structure, DNA damage control, cell cycle regulation, and germinal center reaction. FoxO1 is tightly regulated at a transcriptional (STAT3, HEB, EBF, FoxOs) and post‐transcriptional level (Akt, AMPK, CDK2, GSK3, IKKs, JNK, MAPK/Erk, SGK1, miRNA). In B cell malignancies, recurrent FoxO1 activating mutations (S22/T24) and aberrant nuclear export and activity have been described, underscoring the potential of its therapeutic inhibition. Here, we review FoxO1's roles across B cell and myeloid malignancies, namely acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and multiple myeloma (MM). We also discuss preclinical evidence for FoxO1 targeting by currently available inhibitors (AS1708727, AS1842856, cpd10).

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FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age

Cited by 122 publications

References 63 publications

Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality

Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality

Epigenetic regulation of satellite cell fate during skeletal muscle regeneration

FoxO1 signaling in B cell malignancies and its therapeutic targeting

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