scholarly journals Lactate Metabolism and Satellite Cell Fate

2020 ◽  
Vol 11 ◽  
Author(s):  
Minas Nalbandian ◽  
Zsolt Radak ◽  
Masaki Takeda
Keyword(s):  
Skeletal Muscle ◽  
Cell Fate ◽  
Cell Communication ◽  
Cell Types ◽  
Short Review ◽  
Skeletal Muscle Regeneration ◽  
Metabolic Switch ◽  
Adult Skeletal Muscle

Lactate is one of the metabolic products of glycolysis. It is widely accepted as an important energy source for many cell types and more recently has been proposed to actively participate in cell-cell communication. Satellite cells (SCs), which are adult skeletal muscle stem cells, are the main players of the skeletal muscle regeneration process. Recent studies have proposed a metabolic switch to increase glycolysis in activated SCs. Moreover, lactate has been shown to affect SCs and myoblasts in vivo and in vitro. In this short review, we describe how metabolic variations relate with SC fate (quiescence, activation, proliferation, migration, differentiation, fusion, and self-renewal), as well as discuss possible relationships between lactate as a metabolite and as a signaling molecule affecting SC fate.

scholarly journals Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis

2019 ◽  
Vol 2 (3) ◽  
pp. e201900437 ◽  
Author(s):  
Milica Marinkovic ◽  
Claudia Fuoco ◽  
Francesca Sacco ◽  
Andrea Cerquone Perpetuini ◽  
Giulio Giuliani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Control Mechanism ◽  
Notch Pathway ◽  
Skeletal Muscle Regeneration ◽  
Wild Type ◽  
Adult Skeletal Muscle ◽  
Pathological Conditions ◽  
Dystrophic Mice

Fibro-adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this control mechanism. An unbiased mass spectrometry–based proteomic analysis of FAPs from muscles of wild-type and mdx mice suggested that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. Remarkably, we demonstrated that factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition in mdx FAPs. These results offer a basis for rationalizing pathological ectopic fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fat depositions in muscles of dystrophic patients.

scholarly journals Skeletal muscle fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH-dependent regulation of adipogenesis

2017 ◽  
Author(s):  
Milica Marinkovic ◽  
Francesca Sacco ◽  
Filomena Spada ◽  
Lucia Lisa Petrilli ◽  
Claudia Fuoco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Mass ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Skeletal Muscle Regeneration ◽  
Mdx Mice ◽  
List Type ◽  
Adult Skeletal Muscle

SummaryFibro adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fat infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this control mechanism. Nonetheless, factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition. An unbiased mass spectrometry-based proteomic analysis of FAPs from muscles of wild type and mdx mice, revealed that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. These results offer a basis for rationalizing the pathological outcomes of fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fatty depositions in muscles of dystrophic patients.HighlightsSingle-cell mass cytometry reveals that wt and mdx FAPs are in different cell states.Activation of the NOTCH signaling pathway negatively regulates adipogenesis of wt but not mdx FAPs.Deep proteomics suggests a mechanism explaining the different sensitivity of mdx- FAPs to NOTCH.TNF-a stimulation restores the anti-adipogenic effect of NOTCH in mdx FAPs.

scholarly journals A Promising Future for Stem-Cell-Based Therapies in Muscular Dystrophies—In Vitro and In Vivo Treatments to Boost Cellular Engraftment

2019 ◽  
Vol 20 (21) ◽  
pp. 5433 ◽  
Author(s):  
Daniela Gois Beghini ◽  
Samuel Iwao Horita ◽  
Liana Monteiro da Fonseca Cardoso ◽  
Luiz Anastacio Alves ◽  
Kanneboyina Nagaraju ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Genetic Diseases ◽  
Life Quality ◽  
Cell Types ◽  
Genetic Alterations ◽  
Skeletal Muscle Regeneration ◽  
Muscular Dystrophies

Muscular dystrophies (MD) are a group of genetic diseases that lead to skeletal muscle wasting and may affect many organs (multisystem). Unfortunately, no curative therapies are available at present for MD patients, and current treatments mainly address the symptoms. Thus, stem-cell-based therapies may present hope for improvement of life quality and expectancy. Different stem cell types lead to skeletal muscle regeneration and they have potential to be used for cellular therapies, although with several limitations. In this review, we propose a combination of genetic, biochemical, and cell culture treatments to correct pathogenic genetic alterations and to increase proliferation, dispersion, fusion, and differentiation into new or hybrid myotubes. These boosted stem cells can also be injected into pretreate recipient muscles to improve engraftment. We believe that this combination of treatments targeting the limitations of stem-cell-based therapies may result in safer and more efficient therapies for MD patients. Matricryptins have also discussed.

scholarly journals A Nonerythroid Isoform of Protein 4.1R Interacts with Components of the Contractile Apparatus in Skeletal Myofibers

2000 ◽  
Vol 11 (11) ◽  
pp. 3805-3817 ◽  
Author(s):  
Aikaterini Kontrogianni-Konstantopoulos ◽  
Shu-Ching Huang ◽  
Edward J. Benz
Keyword(s):  
Skeletal Muscle ◽  
Protein S ◽  
Binding Assays ◽  
Adult Skeletal Muscle ◽  
Exon 2 ◽  
Alternatively Spliced ◽  
Translation Initiation Codon ◽  
Protein 4.1R

The ∼80-kDa erythroid 4.1R protein is a major component of the erythrocyte cytoskeleton, where it links transmembrane proteins to the underlying spectrin/actin complexes. A diverse collection of 4.1R isoforms has been described in nonerythroid cells, ranging from ∼30 to ∼210 kDa. In the current study, we identified the number and primary structure of 4.1R isoforms expressed in adult skeletal muscle and characterized the localization patterns of 4.1R message and protein. Skeletal muscle 4.1R appears to originate solely from the upstream translation initiation codon (AUG-1) residing in exon 2′. Combinations of alternatively spliced downstream exons generate an array of distinct 4.1R spliceoforms. Two major isoform classes of ∼105/110 and ∼135 kDa are present in muscle homogenates. 4.1R transcripts are distributed in highly ordered signal stripes, whereas 4.1R protein(s) decorate the sarcoplasm in transverse striations that are in register with A-bands. An ∼105/110-kDa 4.1R isoform appears to occur in vivo in a supramolecular complex with major sarcomeric proteins, including myosin, α-actin, and α-tropomyosin. In vitro binding assays showed that 4.1R may interact directly with the aforementioned contractile proteins through its 10-kDa domain. All of these observations suggest a topological model whereby 4.1R may play a scaffolding role by anchoring the actomyosin myofilaments and possibly modulating their displacements during contraction/relaxation.

scholarly journals Molecular Targets of Androgen Signaling that Characterize Skeletal Muscle Recovery and Regeneration

2015 ◽  
Vol 13 (1) ◽  
pp. nrs.13005 ◽  
Author(s):  
James G. MacKrell ◽  
Benjamin C. Yaden ◽  
Heather Bullock ◽  
Keyue Chen ◽  
Pamela Shetler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Targets ◽  
Gene Signature ◽  
Muscle Recovery ◽  
In Vivo Models ◽  
Adult Skeletal Muscle ◽  
Injury Model ◽  
Androgen Regulation

The high regenerative capacity of adult skeletal muscle relies on a self-renewing depot of adult stem cells, termed muscle satellite cells (MSCs). Androgens, known mediators of overall body composition and specifically skeletal muscle mass, have been shown to regulate MSCs. The possible overlapping function of androgen regulation of muscle growth and MSC activation has not been carefully investigated with regards to muscle regeneration. Therefore, the aim of this study was to examine coinciding androgen-mediated genetic changes in an in vitro MSC model and clinically relevant in vivo models. A gene signature was established via microarray analysis for androgen-mediated MSC engagement and highlighted several markers including follistatin (FST), IGF-1, C-X-C chemokine receptor 4 (CXCR4), hepatocyte growth factor (HGF) and glucocorticoid receptor (GR/Nr3c1). In an in vivo muscle atrophy model, androgen re-supplementation significantly increased muscle size and expression of IGF-1, FST, and HGF, while significantly decreasing expression of GR. Biphasic gene expression profiles over the 7-day re-supplementation period identifed temporal androgen regulation of molecular targets involved in satellite cell engagement into myogenesis. In a muscle injury model, removal of androgens resulted in delayed muscle recovery and regeneration. Modifications in the androgen signaling gene signature, along with reduced Pax7 and MyoD expression, suggested that limited MSC activation and increased inflammation contributed to the delayed regeneration. However, enhanced MSC activation in the androgen-deplete mouse injury model was driven by an androgen receptor (AR) agonist. These results provide novel in vitro and in vivo evidence describing molecular targets of androgen signaling, while also increasing support for translational use of AR agonists in skeletal muscle recovery and regeneration.

scholarly journals FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis

2021 ◽  
Vol 118 (37) ◽  
pp. e2021013118 ◽  
Author(s):  
Sebastian Mathes ◽  
Alexandra Fahrner ◽  
Umesh Ghoshdastider ◽  
Hannes A. Rüdiger ◽  
Michael Leunig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Human Skeletal Muscle ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Adeno Associated Virus ◽  
Adult Skeletal Muscle

Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus–mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2–dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle.

scholarly journals PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells

2015 ◽  
Vol 309 (3) ◽  
pp. C159-C168 ◽  
Author(s):  
Tsung-Chuan Ho ◽  
Yi-Pin Chiang ◽  
Chih-Kuang Chuang ◽  
Show-Li Chen ◽  
Jui-Wen Hsieh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Satellite Cell Proliferation

In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser93-Leu112) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2′-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration.

Advances and Challenges in Kidney Organoids

2021 ◽  
Vol 16 ◽  
Author(s):  
Vikram Sabapathy ◽  
Gabrielle Costlow ◽  
Rajkumar Venkatadri ◽  
Murat Dogan ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Complex Structures ◽  
Cell Culture Systems ◽  
Epigenetic Signatures ◽  
Kidney Organoids

: The advent of organoids has renewed researcher's interest in in vitro cell culture systems. A wide variety of protocols, primarily utilizing pluripotent stem cells, are under development to improve organoid generation to mimic organ development. The complexity of organoids generated is greatly influenced based on the method used. Understanding the process of kidney organoid formation gives developmental insights into how renal cells form, mature, and interact with the adjacent cells to form specific spatiotemporal structural patterns. This knowledge can bridge the gaps in understanding in vivo renal developmental processes. Evaluating genetic and epigenetic signatures in specialized cell types can help interpret the molecular mechanisms governing cell fate. In addition, development in single-cell RNA sequencing and 3D bioprinting and microfluidic technologies has led to better identification and understanding of a variety of cell types during differentiation and designing of complex structures to mimic the conditions in vivo. While several reviews have highlighted the application of kidney organoids, there is no comprehensive review of various methodologies specifically focusing on the kidney organoids. This review summarizes the updated differentiation methodologies, applications, and challenges associated with kidney organoids. Here we have comprehensively collated all the different variables influencing the organoid generation.

Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3637-3650 ◽  
Author(s):  
C.P. Austin ◽  
D.E. Feldman ◽  
J.A. Ida ◽  
C.L. Cepko
Keyword(s):  
Cell Fate ◽  
Ganglion Cells ◽  
Notch Pathway ◽  
Cell Types ◽  
Projection Neurons ◽  
Specific Cell ◽  
Vitro Assay ◽  
Notch Activity

The first cells generated during development of the vertebrate retina are the ganglion cells, the projection neurons of the retina. Although they are one of the most intensively studied cell types within the central nervous system, little is known of the mechanisms that determine ganglion cell fate. We demonstrate that ganglion cells are selected from a large group of competent progenitors that comprise the majority of the early embryonic retina and that differentiation within this group is regulated by Notch. Notch activity in vivo was diminished using antisense oligonucleotides or augmented using a retrovirally transduced constitutively active allele of Notch. The number of ganglion cells produced was inversely related to the level of Notch activity. In addition, the Notch ligand Delta inhibited retinal progenitors from differentiating as ganglion cells to the same degree as did activated Notch in an in vitro assay. These results suggest a conserved strategy for neurogenesis in the retina and describe a versatile in vitro and in vivo system with which to examine the action of the Notch pathway in a specific cell fate decision in a vertebrate.

scholarly journals Conditional Deletion of Dicer in Adult Mice Impairs Skeletal Muscle Regeneration

2019 ◽  
Vol 20 (22) ◽  
pp. 5686 ◽  
Author(s):  
Satoshi Oikawa ◽  
Minjung Lee ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Tibialis Anterior Muscle ◽  
Critical Factor ◽  
Skeletal Muscle Regeneration ◽  
Small Noncoding Rnas ◽  
Adult Mice

Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7+ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo.

Sign in / Sign up

Export Citation Format

Share Document