scholarly journals Zeb2 Regulates Myogenic Differentiation in Pluripotent Stem Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2525
Author(s):  
Ester Sara Di Filippo ◽  
Domiziana Costamagna ◽  
Giorgia Giacomazzi ◽  
Álvaro Cortés-Calabuig ◽  
Agata Stryjewska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Differentiation ◽  
E Box

Skeletal muscle differentiation is triggered by a unique family of myogenic basic helix-loop-helix transcription factors, including MyoD, MRF-4, Myf-5, and Myogenin. These transcription factors bind promoters and distant regulatory regions, including E-box elements, of genes whose expression is restricted to muscle cells. Other E-box binding zinc finger proteins target the same DNA response elements, however, their function in muscle development and regeneration is still unknown. Here, we show that the transcription factor zinc finger E-box-binding homeobox 2 (Zeb2, Sip-1, Zfhx1b) is present in skeletal muscle tissues. We investigate the role of Zeb2 in skeletal muscle differentiation using genetic tools and transgenic mouse embryonic stem cells, together with single-cell RNA-sequencing and in vivo muscle engraftment capability. We show that Zeb2 over-expression has a positive impact on skeletal muscle differentiation in pluripotent stem cells and adult myogenic progenitors. We therefore propose that Zeb2 is a novel myogenic regulator and a possible target for improving skeletal muscle regeneration. The non-neural roles of Zeb2 are poorly understood.

scholarly journals Sharp-1/DEC2 Inhibits Skeletal Muscle Differentiation through Repression of Myogenic Transcription Factors

2004 ◽  
Vol 279 (50) ◽  
pp. 52643-52652 ◽  
Author(s):  
Sameena Azmi ◽  
Anne Ozog ◽  
Reshma Taneja
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Myogenic Differentiation ◽  
Constitutive Expression ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
E Proteins ◽  
C2c12 Myoblasts ◽  
E Box ◽  
Bhlh Factors

Skeletal muscle differentiation is regulated by the basic-helix-loop-helix (bHLH) family of transcription factors. The myogenic bHLH factors form heterodimers with the ubiquitously expressed bHLH E-proteins and bind E-box (CANNTG) sites present in the promoters of several muscle-specific genes. Our previous studies have shown that the bHLH factor Sharp-1 is expressed in skeletal muscle and interacts with MyoD and E-proteins. However, its role in regulation of myogenic differentiation remains unknown. We report here that endogenous Sharp-1 is expressed in proliferating C2C12 myoblasts and is down-regulated during myogenic differentiation. Constitutive expression of Sharp-1 in C2C12 myoblasts promotes cell cycle exit causing a decrease in cyclin D1 expression but blocks terminal differentiation. Although MyoD expression is not inhibited, the induction of differentiation-specific genes such as myogenin, MEF2C, and myosin heavy chain is impaired by Sharp-1 overexpression. We demonstrate that the interaction of Sharp-1 with MyoD and E-proteins results in reduced DNA binding and transactivation from MyoD-dependent E-box sites. Re-expression of MyoD∼E47 rescues the differentiation defect imposed by Sharp-1, suggesting that myogenic bHLH factors function downstream of Sharp-1. Our data suggest that protein-protein interactions between Sharp-1, MyoD, and E47 resulting in interference with MyoD function underlies Sharp-1-mediated repression of myogenic differentiation.

Pluripotent Stem Cells and Skeletal Muscle Differentiation: Challenges and Immediate Applications

2017 ◽  
pp. 1-35
Author(s):  
Elena Garreta ◽  
Andrés Marco ◽  
Cristina Eguizábal ◽  
Carolina Tarantino ◽  
Mireia Samitier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation

scholarly journals Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis

2019 ◽  
Vol 27 (5) ◽  
pp. 1644-1659 ◽  
Author(s):  
Yaping Nie ◽  
Shufang Cai ◽  
Renqiang Yuan ◽  
Suying Ding ◽  
Xumeng Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zinc Finger ◽  
Muscle Development ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Finger Protein

Abstract Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.

scholarly journals Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shinichiro Hayashi ◽  
Ichiro Manabe ◽  
Yumi Suzuki ◽  
Frédéric Relaix ◽  
Yumiko Oishi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Biological Processes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Acting In Concert

Krüppel-like factor 5 (Klf5) is a zinc-finger transcription factor that controls various biological processes, including cell proliferation and differentiation. We show that Klf5 is also an essential mediator of skeletal muscle regeneration and myogenic differentiation. During muscle regeneration after injury (cardiotoxin injection), Klf5 was induced in the nuclei of differentiating myoblasts and newly formed myofibers expressing myogenin in vivo. Satellite cell-specific Klf5 deletion severely impaired muscle regeneration, and myotube formation was suppressed in Klf5-deleted cultured C2C12 myoblasts and satellite cells. Klf5 knockdown suppressed induction of muscle differentiation-related genes, including myogenin. Klf5 ChIP-seq revealed that Klf5 binding overlaps that of MyoD and Mef2, and Klf5 physically associates with both MyoD and Mef2. In addition, MyoD recruitment was greatly reduced in the absence of Klf5. These results indicate that Klf5 is an essential regulator of skeletal muscle differentiation, acting in concert with myogenic transcription factors such as MyoD and Mef2.

scholarly journals MyoD-positive epiblast cells regulate skeletal muscle differentiation in the embryo

2006 ◽  
Vol 175 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Jacquelyn Gerhart ◽  
Justin Elder ◽  
Christine Neely ◽  
Jared Schure ◽  
Tage Kvist ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Body Wall ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Stem Cells ◽  
Skeletal Muscle Stem Cells

MyoD mRNA is expressed in a subpopulation of cells within the embryonic epiblast. Most of these cells are incorporated into somites and synthesize Noggin. Ablation of MyoD-positive cells in the epiblast subsequently results in the herniation of organs through the ventral body wall, a decrease in the expression of Noggin, MyoD, Myf5, and myosin in the somites and limbs, and an increase in Pax-3–positive myogenic precursors. The addition of Noggin lateral to the somites compensates for the loss of MyoD-positive epiblast cells. Skeletal muscle stem cells that arise in the epiblast are utilized in the somites to promote muscle differentiation by serving as a source of Noggin.

scholarly journals MEF2 Transcription Factors Regulate Distinct Gene Programs in Mammalian Skeletal Muscle Differentiation

2014 ◽  
Vol 290 (2) ◽  
pp. 1256-1268 ◽  
Author(s):  
Nelsa L. Estrella ◽  
Cody A. Desjardins ◽  
Sarah E. Nocco ◽  
Amanda L. Clark ◽  
Yevgeniy Maksimenko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Muscle Differentiation ◽  
Mammalian Skeletal Muscle ◽  
Skeletal Muscle Differentiation ◽  
Distinct Gene

scholarly journals MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1

2021 ◽  
Author(s):  
Paromita Dey ◽  
Miles A Soyer ◽  
Bijan K Dey
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior Muscle ◽  
High Mobility ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Stem Cells ◽  
Downstream Target

Abstract Numerous studies have established the critical roles of microRNAs in regulating posttranscriptional gene expression in diverse biological processes. Here, we report on the role and mechanism of miR-24-3p in skeletal muscle differentiation and regeneration. miR-24-3p promotes myoblast differentiation and skeletal muscle regeneration by directly targeting high mobility group AT-hook 1 (HMGA1) and regulating it and its direct downstream target, the inhibitor of differentiation 3 (ID3). miR-24-3p knockdown in neonatal mice increases PAX7-positive proliferating muscle stem cells (MuSCs) by derepressing Hmga1 and Id3 . Similarly, inhibiting miR24-3p in the tibialis anterior muscle prevents Hmga1 and Id3 downregulation and impairs regeneration. These findings provide evidence that the miR-24-3p/HMGA1/ID3 axis is required for MuSC differentiation and regeneration in vivo .

scholarly journals 6-Bromoindirubin-3′-oxime intercepts GSK3 signaling to promote and enhance skeletal muscle differentiation affecting miR-206 expression in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elvira Ragozzino ◽  
Mariarita Brancaccio ◽  
Antonella Di Costanzo ◽  
Francesco Scalabrì ◽  
Gennaro Andolfi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Skeletal Muscle Differentiation ◽  
Myoblast Proliferation ◽  
Enhanced Expression ◽  
Pharmacologically Active

AbstractDystrophies are characterized by progressive skeletal muscle degeneration and weakness as consequence of their molecular abnormalities. Thus, new drugs for restoring skeletal muscle deterioration are critically needed. To identify new and alternative compounds with a functional role in skeletal muscle myogenesis, we screened a library of pharmacologically active compounds and selected the small molecule 6-bromoindirubin-3′-oxime (BIO) as an inhibitor of myoblast proliferation. Using C2C12 cells, we examined BIO’s effect during myoblast proliferation and differentiation showing that BIO treatment promotes transition from cell proliferation to myogenic differentiation through the arrest of cell cycle. Here, we show that BIO is able to promote myogenic differentiation in damaged myotubes in-vitro by enriching the population of newly formed skeletal muscle myotubes. Moreover, in-vivo experiments in CTX-damaged TA muscle confirmed the pro-differentiation capability of BIO as shown by the increasing of the percentage of myofibers with centralized nuclei as well as by the increasing of myofibers number. Additionally, we have identified a strong correlation of miR-206 with BIO treatment both in-vitro and in-vivo: the enhanced expression of miR-206 was observed in-vitro in BIO-treated proliferating myoblasts, miR-206 restored expression was observed in a forced miR-206 silencing conditions antagomiR-mediated upon BIO treatment, and in-vivo in CTX-injured muscles miR-206 enhanced expression was observed upon BIO treatment. Taken together, our results highlight the capacity of BIO to act as a positive modulator of skeletal muscle differentiation in-vitro and in-vivo opening up a new perspective for novel therapeutic targets to correct skeletal muscle defects.

scholarly journals Skeletal Muscle Cell Induction from Pluripotent Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Yusaku Kodaka ◽  
Gemachu Rabu ◽  
Atsushi Asakura
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Cell ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Embryonic Stem ◽  
Muscle Cells ◽  
Skeletal Muscle Cell ◽  
Skeletal Muscle Cells ◽  
Cell Induction

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD). Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

Sign in / Sign up

Export Citation Format

Share Document