Cellular function of satellite cells does not play a role in muscle weakness of adult Ts1Cje mice
Down syndrome (DS) is a genetic condition resulting from triplication of human chromosome (HSA)21. Besides intellectual disability, DS is frequently associated with hypotonia. Satellite cells are the resident cells that provides robust and remarkable regenerative capacity to the skeletal muscles, and its population size has been reported to be disease-associated. However, little is known about the population size of satellite cells in DS and the association of its intrinsic cellular functionality and hypotonia seen in DS. Here, we studied the Ts1Cje mouse, a DS murine model displays the muscle weakness characteristic. Satellite cell populations were immunostained with Pax7 and myonuclei numbers in the Ts1Cje extensor digitorum longus muscle were assessed. Their cellular function was further determined via in vitro assay in high-serum conditioned medium. Subsequently, the in vitro self-renewal, proliferative, and differentiation activities of these myogenic precursor cells were assessed after 24, 48, and 72h using Pax7, MyoD, and Ki67 immunomarkers. Our results showed that the population and functionality of Ts1Cje satellite cell did not differ significantly when compared to the wildtype cells isolated from disomic littermates. In conclusion, our findings indicate that intrinsic cellular functionality of the satellite cells, do not contribute to muscle weakness in Ts1Cje mouse.
Allen D.L., Roy R.R., Edgerton V.R. Myonuclear domains in muscle adaptation and disease. Muscle Nerve 1999, 22: 1350-1360. https://www.ncbi.nlm.nih.gov/pubmed/10487900
Boldrin L., Morgan J.E. Human satellite cells: identification on human muscle fibres. PLoS Curr 2013, 3: RRN1294. https://doi.org/10.1371/currents.RRN1294
Brack A.S. Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy. J Cell Sci 2005, 118: 4813-4821. https://doi.org/10.1242/jcs.02602
Brault V., Duchon A., Romestaing C., Sahun I., Pothion S., Karout M., et al. Opposite phenotypes of muscle strength and locomotor function in mouse models of partial trisomy and monosomy 21 for the proximal Hspa13-App region. PLOS Genet 2015, 11: e1005062. https://doi.org/10.1371/journal.pgen.1005062
Cowley P.M., Keslacy S., Middleton F.A., DeRuisseau L.R., Fernhall B., Kanaley J.A., DeRuisseau K.C. Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition. Am J Physiol Regul Integr Comp Physiol 2012, 303: R1251-R1260. https://doi.org/10.1152/ajpregu.00312.2012
Dumont N.A., Wang Y.X., Rudnicki M.A. Intrinsic and extrinsic mechanisms regulating satellite cell function. Development 2015, 142: 1572-1581. https://doi.org/10.1242/dev.114223
Jang Y.C., Sinha M., Cerletti M., Dall'Osso C., Wagers A.J. Skeletal muscle stem cells: effects of aging and metabolism on muscle regenerative function. Cold Spring Harb Symp Quant Biol 2011, 76: 101-111. https://doi.org/10.1101/sqb.2011.76.010652
Koopman R., Ly C.H., Ryall J.G. A metabolic link to skeletal muscle wasting and regeneration. Front Physiol 2014, 5: 32. https://doi.org/10.3389/fphys.2014.00032
Lim C.L., Ling K.H., Cheah P.S. Isolation, cultivation and immunostaining of single myofibers- an improved approach to study the behaviour of satellite cells. J Biol Methods 2018, 5: e87. https://doi.org/10.14440/jbm.2018.219
Ling K.H., Hewitt C.A., Tan K.L., Cheah P.S., Vidyadaran S., Lai M.I., et al. Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks. BMC Genomics 2014, 15: 624. https://doi.org/10.1186/1471-2164-15-624
Lisi E.C., Cohn R.D. Genetic evaluation of the pediatric patient with hypotonia: perspective from a hypotonia specialty clinic and review of the literature. Dev Med Child Neurol 2011, 53: 586-599. https://doi.org/10.1111/j.1469-8749.2011.03918.x
Liu B., Filippi S., Roy A., Roberts I. Stem and progenitor cell dysfunction in human trisomies. EMBO Rep 2015, 16: 44-62. https://doi.org/10.15252/embr.201439583
National Center on Birth Defects and Developmental Disabilities (NCBDDD) | CDC. National Center on Birth Defects and Developmental Disabilities Home | NCBDDD | CDC. 2017. Available at: http://www.cdc.gov/ncbddd/birthdefects/downsyndrome.html. Accessed May 26, 2017.
Neal A., Boldrin L., Morgan J.E. The satellite cell in male and female, developing and adult mouse muscle: distinct stem cells for growth and regeneration. PLoS ONE 2012, 7: e37950. https://doi.org/10.1371/journal.pone.0037950
Roper R.J., Reeves R.H. Understanding the basis for Down syndrome phenotypes. PLoS Genet 2006, 2: e50. https://doi.org/10.1371/journal.pgen.0020050
Sago H., Carlson E., Smith D., Kilbridge J., Rubin E., Mobley W.C., Epstein C.J., Huang T.T. Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proc Natl Acad Sci USA 1998, 95: 6256-6261. https://www.ncbi.nlm.nih.gov/pubmed/9600952
Schlüter C., Duchrow M., Wohlenberg C., Becker M.H., Key G., Flad H.D., et al. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol 1993, 123: 513-522. https://doi.org/10.1083/jcb.123.3.513
Shefer G., Rauner G., Yablonka-Reuveni Z., Benayahu D. Reduced satellite cell numbers and myogenic capacity in aging can be alleviated by endurance exercise. PLoS ONE 2010, 5: e13307. https://doi.org/10.1371/journal.pone.0013307
Shefer G., Van de Mark D.P., Richardson J.B., Yablonka-Reuveni Z. Satellite-cell pool size does matter: Defining the myogenic potency of aging skeletal muscle. Dev Biol 2006, 294: 50-66. https://doi.org/10.1016/j.ydbio.2006.02.022
Shimohata A., Ishihara K., Hattori S., Miyamoto H., Morishita H., Ornthanalai G., Raveau M., Ebrahim A.S., Amano K., Yamada K., Sago H., Akiba S., Mataga N., Murphy N.P., Miyakawa T., Yamakawa K. Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism. Exp Neurol. 2017, 293: 1-12. https://doi.org/10.1016/j.expneurol.2017.03.009
Tierney M.T., Sacco A. The role of muscle stem cell-niche interactions during aging. Nat Med 2016, 22: 837-838. https://doi.org/10.1038/nm.4159
Van der Meer S.F., Jaspers R.T., Degens H. Is the myonuclear domain size fixed? J Musculoskelet Neuronal Interact 2011, 11: 286-297. https://www.ncbi.nlm.nih.gov/pubmed/22130137
Yin H., Price F., Rudnicki M. Satellite cells and the muscle stem cell niche. Physiol Rev 2013, 93: 23-67. https://doi.org/10.1152/physrev.00043.2011
Zammit P.S., Golding J.P., Nagata Y., Hudon V., Partridge T.A., Beauchamp J.R. Muscle satellite cells adopt divergent fates. J Cell Biol 2004, 166:347-357. https://doi.org/10.1083/jcb.200312007
Copyright (c) 2018 Chai Ling Lim, Usman Bala, Melody Pui-Yee Leong, Johnson Stanslas, Rajesh Ramasamy, King Hwa Ling, Pike See Cheah
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The observations and associated materials published or posted by NeurosciRN are licensed by the authors for use and distribution in accord with the Creative Commons Attribution license CC BY-NC 4.0 international, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.