scholarly journals SIX1 and SIX4 homeoproteins regulate PAX7+ progenitor cell properties during fetal epaxial myogenesis

Development ◽  
2020 ◽  
Vol 147 (19) ◽  
pp. dev185975
Author(s):  
Maud Wurmser ◽  
Nathalie Chaverot ◽  
Rouba Madani ◽  
Hiroshi Sakai ◽  
Elisa Negroni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Skeletal Muscles ◽  
Progenitor Cell ◽  
Tibialis Anterior Muscle ◽  
Muscle Growth ◽  
Genetic Determinants ◽  
Sine Oculis ◽  
Myogenic Stem Cells ◽  
Cell Position ◽  
Myogenic Program

ABSTRACTPax7 expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the sine oculis-related homeobox Six1-Six6 genes in vertebrates. Six1, Six2, Six4 and Six5 are expressed in the muscle lineage. Here, we tested the hypothesis that Six1 and Six4 could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in Six1 and Six4 knockout mice (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior muscle. Mutant stem cells contribute to hypotrophic myofibers that are not innervated but retain the ability to self-renew.

scholarly journals Loss of Ptpn11 (Shp2) drives satellite cells into quiescence

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Joscha Griger ◽  
Robin Schneider ◽  
Ines Lahmann ◽  
Verena Schöwel ◽  
Charles Keller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tyrosine Phosphatase ◽  
Muscle Growth ◽  
Cell Activity ◽  
Muscle Stem Cells ◽  
Myogenic Stem Cells ◽  
Postnatal Myogenesis ◽  
Receptor Tyrosine Phosphatase ◽  
Satellite Cell Activity

The equilibrium between proliferation and quiescence of myogenic progenitor and stem cells is tightly regulated to ensure appropriate skeletal muscle growth and repair. The non-receptor tyrosine phosphatase Ptpn11 (Shp2) is an important transducer of growth factor and cytokine signals. Here we combined complex genetic analyses, biochemical studies and pharmacological interference to demonstrate a central role of Ptpn11 in postnatal myogenesis of mice. Loss of Ptpn11 drove muscle stem cells out of the proliferative and into a resting state during muscle growth. This Ptpn11 function was observed in postnatal but not fetal myogenic stem cells. Furthermore, muscle repair was severely perturbed when Ptpn11 was ablated in stem cells due to a deficit in stem cell proliferation and survival. Our data demonstrate a molecular difference in the control of cell cycle withdrawal in fetal and postnatal myogenic stem cells, and assign to Ptpn11 signaling a key function in satellite cell activity.

Myoid cell density in the thymus is reduced during mdx dystrophy and after muscle crush

1999 ◽  
Vol 77 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Annyue Wong ◽  
Kerryn L Garrett ◽  
Judy E Anderson
Keyword(s):  
Stem Cells ◽  
Cell Density ◽  
Troponin T ◽  
Tibialis Anterior Muscle ◽  
Fiber Formation ◽  
Myoid Cells ◽  
Myoid Cell ◽  
Developmental Age ◽  
Myogenic Stem Cells ◽  
Thymic Myoid Cells

Thymic myoid cells share structural and behavioural features with cells of the skeletal muscle lineage: they express regulatory genes and contractile proteins, and they can form myofibers in culture. Historically, those features suggested that myoid cells could be precursors for muscle repair in addition to the satellite cells in muscle that are typically designated as the only muscle precursors. Muscles of the mutant mdx dystrophic mouse strain have a large demand for precursors, which is greatest at a young age. In the present study, immunostaining for troponin T was used to localize myoid cells. We tested the hypothesis that the myoid cell population changes when there is a demand for muscle precursors and that these changes would be anticipated if myoid cells have a role as myogenic precursors or stem cells in muscle. Chronic demands for muscle precursors in mdx dystrophic mice were accompanied by lower myoid cell density in comparison with density in two normal strains (C57BL10/ScSn and Swiss Webster). Acute demand for precursors was accompanied by a sharp decline in thymic myoid cell density within 2 days after a crush injury to one tibialis anterior muscle in normal but not dystrophic animals. To standardize the developmental age of the thymus, density was determined in all animals at 28 days of age. Given the current interest in nonmuscle sources of myogenic stem cells, these data suggest that changes in the density of thymic myoid cells may accompany acute and chronic demands for muscle precursors. Further experiments are required to determine whether thymic myoid cells are participants in distant muscle cell proliferation, new fiber formation, or the establishment of new stem cells in regenerated muscle.Key words: thymus, myoid cells, troponin T, MyoD, tissue repair, myoblasts, mdx dystrophy.

scholarly journals Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

Epigenomes ◽  
2018 ◽  
Vol 2 (3) ◽  
pp. 13
Author(s):  
José Belizário
Keyword(s):  
Stem Cells ◽  
Skeletal Muscles ◽  
Small Population ◽  
Epigenetic Mechanisms ◽  
Cancer Risks ◽  
Mutational Signatures ◽  
Environmental Agents ◽  
Risk Of Malignancy ◽  
The Brain ◽  
Cellular Genome

Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.

Differentiation-related changes in myogenic stem cells

Biologija ◽  
2010 ◽  
Vol 56 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Laima Degutytė-Fomins ◽  
Rasa Žūkienė ◽  
Odeta Buzaitė ◽  
Paulius Dzikas ◽  
Zita Naučienė ◽  
...  
Keyword(s):  
Stem Cells ◽  
Myogenic Stem Cells

Heterogeneity in histone 2B-green fluorescent protein-retaining putative small intestinal stem cells at cell position 4 and their absence in the colon

2012 ◽  
Vol 303 (11) ◽  
pp. G1188-G1201 ◽  
Author(s):  
Kevin R. Hughes ◽  
Ricardo M. C. Gândara ◽  
Tanvi Javkar ◽  
Fred Sablitzky ◽  
Hanno Hock ◽  
...  
Keyword(s):  
Stem Cells ◽  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Paneth Cells ◽  
Epithelial Stem Cells ◽  
Epithelial Regeneration ◽  
Cell Position ◽  
Small Intestinal ◽  
Green Fluorescent ◽  
Dose Radiation

Stem cells have been identified in two locations in small intestinal crypts; those intercalated between Paneth cells and another population (which retains DNA label) are located above the Paneth cell zone, at cell position 4. Because of disadvantages associated with the use of DNA label, doxycycline-induced transient transgenic expression of histone 2B (H2B)-green fluorescent protein (GFP) was investigated. H2B-GFP-retaining putative stem cells were consistently seen, with a peak at cell position 4, over chase periods of up to 112 days. After a 28-day chase, a subpopulation of the H2B-GFP-retaining cells was cycling, but the slow cycling status of the majority was illustrated by lack of expression of pHistone H3 and Ki67. Although some H2B-GFP-retaining cells were sensitive to low-dose radiation, the majority was resistant to low- and high-dose radiation-induced cell death, and a proportion of the surviving cells proliferated during subsequent epithelial regeneration. Long-term retention of H2B-GFP in a subpopulation of small intestinal Paneth cells was also seen, implying that they are long lived. In contrast to the small intestine, H2B-GFP-retaining epithelial cells were not seen in the colon from 28-day chase onward. This implies important differences in stem cell function between these two regions of the gastrointestinal tract, which may have implications for region-specific susceptibility to diseases (such as cancer and ulcerative colitis), in which epithelial stem cells and their progeny are involved.

scholarly journals Effects of Aging on Angiogenic and Muscle Growth-Related Factors in Naturally Aged Rat Skeletal Muscles

2020 ◽  
Vol 24 (4) ◽  
pp. 305-312
Author(s):  
Hyo-Seong Yeo ◽  
Jae-Young Lim ◽  
Na-Young Ahn
Keyword(s):  
Skeletal Muscles ◽  
Muscle Growth ◽  
Related Factors ◽  
Aged Rat ◽  
Effects Of Aging

scholarly journals The microRNA, miR-133b, functions to slow Duchenne muscular dystrophy pathogenesis

2020 ◽  
Author(s):  
Thomas Taetzsch ◽  
Dillon Shapiro ◽  
Randa Eldosougi ◽  
Tracey Myers ◽  
Robert Settlage ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Skeletal Muscles ◽  
Tibialis Anterior Muscle ◽  
Muscle Fibers ◽  
Progressive Degeneration ◽  
Protein Encoding ◽  
Small Muscle ◽  
Encoding Genes

AbstractDuchenne muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal muscles. To date, there are no treatments available to slow or prevent the disease. Hence, it remains essential to identify molecular factors that promote muscle biogenesis since they could serve as therapeutic targets for treating DMD. While the muscle enriched microRNA, miR-133b, has been implicated in the biogenesis of muscle fibers, its role in DMD remains unknown. To assess the role of miR-133b in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers with centralized nuclei, exhibits increased fibrosis, and thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering the number of satellite cells and levels of protein-encoding genes, including previously identified miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.

scholarly journals Differentiation of Human Embryonic Stem Cells into Engrafting Myogenic Precursor Cells

2019 ◽  
Vol 1 (1) ◽  
pp. 01-05
Author(s):  
Stalin Reddy Challa ◽  
Swathi Goli
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Precursor Cells ◽  
Functional Improvement ◽  
Serum Free ◽  
Myogenic Stem Cells ◽  
Serum Free Conditions ◽  
Myogenic Precursor

Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.

scholarly journals Accessibility Over Transposable Elements Reveals Genetic Determinants of Stemness Properties in Normal and Leukemic Hematopoiesis

2021 ◽  
Author(s):  
Bettina Nadorp ◽  
Giacomo Grillo ◽  
Aditi Qamra ◽  
Amanda Mitchell ◽  
Christopher Arlidge ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Chromatin Accessibility ◽  
Genetic Determinants ◽  
Hematopoietic Stem ◽  
Transcription Regulators ◽  
Docking Sites ◽  
Cellular Hierarchy ◽  
Mutational Processes

AbstractDespite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two thirds of patients will relapse with fatal disease within 5 years. AML is organized as a cellular hierarchy sustained by leukemia stem cells (LSC) at the apex, with LSC properties directly linked to tumor progression, therapy failure and disease relapse 1–5. Despite the central role of LSC in poor patient outcomes, little is known of the genetic determinants of their stemness properties 6–8. Although much AML research focuses on mutational processes and their impact on gene expression programs, the genetic determinants of cell state properties including stemness expand beyond mutations, relying on the genetic architecture captured in the chromatin of each cell 9–11. As LSCs share many functional and molecular properties with normal hematopoietic stem cells (HSC), we identified genetic determinants of primitive populations enriched for LSCs and HSCs in comparison with their downstream mature progeny by investigating their chromatin accessibility. Our work reveals how distinct transposable element (TE) subfamilies are used in primitive versus mature populations, functioning as docking sites for stem cell-associated regulators of genome topology, including CTCF, or lineage-specific transcription regulators in primitive and mature populations, respectively. We further show how TE subfamilies accessible in LSCs define docking sites for several oncogenic drivers in AML, namely FLI1, LYL1 and MEIS1. Using chromatin accessibility profiles from a cohort of AML patients, we further show the clinical utility of our TE accessibility-based LSCTE121 scoring scheme to identify patients with high rates of relapse. Collectively, our work reveals how different accessible TE subfamilies serve as genetic determinants of stemness properties in normal and leukemic hematopoietic stem cells.

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