Dataset Information

Skeletal Muscle Subpopulation Rearrangements upon Rhabdomyosarcoma Development through Single-Cell Mass Cytometry.

ABSTRACT: The embryonal rhabdomyosarcoma (eRMS) is a soft tissue sarcoma commonly affecting the head and neck, the extremities and the genitourinary tract. To contribute to revealing the cell types that may originate this tumor, we exploited mass cytometry, a single-cell technique that, by using heavy-metal-tagged antibodies, allows the accurate monitoring of the changes occurring in the mononuclear cell composition of skeletal muscle tissue during tumor development. To this end, we compared cell populations of healthy muscles with those from spatiotemporal-induced eRMS tumors in a mouse model (LSL-Kras^G12D/+;Tp53^Fl/Fl) that can be used to develop rhabdomyosarcoma by means of infection with an adenovirus vector expressing Cre (Ad-Cre) recombinase. By monitoring different time points after tumor induction, we were able to analyze tumor progression and composition, identifying fibro/adipogenic progenitors (FAPs) as the cell type that, in this model system, had a pivotal role in tumor development. In vitro studies highlighted that both FAPs and satellite cells (SCs), upon infection with the Ad-Cre, acquired the potential to develop rhabdomyosarcomas when transplanted into immunocompromised mice. However, only infected FAPs had an antigen profile that was similar to embryonal rhabdomyosarcoma cells. Overall, our analysis supports the involvement of FAPs in eRMS development.

SUBMITTER: Petrilli LL

PROVIDER: S-EPMC7922544 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Skeletal Muscle Subpopulation Rearrangements upon Rhabdomyosarcoma Development through Single-Cell Mass Cytometry.

Petrilli Lucia Lisa LL Riccio Federica F Giuliani Giulio G Palma Alessandro A Gargioli Cesare C Vumbaca Simone S Faron Monika M Palmieri Graziana G Pasquini Luca L Sacco Francesca F Cesareni Gianni G Castagnoli Luisa L Fuoco Claudia C

Journal of clinical medicine 20210217 4

The embryonal rhabdomyosarcoma (eRMS) is a soft tissue sarcoma commonly affecting the head and neck, the extremities and the genitourinary tract. To contribute to revealing the cell types that may originate this tumor, we exploited mass cytometry, a single-cell technique that, by using heavy-metal-tagged antibodies, allows the accurate monitoring of the changes occurring in the mononuclear cell composition of skeletal muscle tissue during tumor development. To this end, we compared cell populati ...[more]

PMID: 33671425

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Project description:BackgroundAerobic exercise has been proven to have a positive effect on cardiac function after hypertension; however, the mechanism is not entirely clarified. Skeletal muscle mass and microcirculation are closely associated with blood pressure and cardiac function.ObjectiveThis study was designed to investigate the effects of aerobic exercise on the skeletal muscle capillary and muscle mass, to explore the possible mechanisms involved in exercise-induced mitigation of cardiac dysfunction in pressure overload mice.MethodsIn this study, 60 BALB/C mice aged 8 weeks were randomly divided into 3 groups: control (CON), TAC, and TAC plus exercise (TAE) group and utilized transverse aortic constriction (TAC) to establish hypertensive model; meanwhile, treadmill training is used for aerobic exercise. After 5 days of recovery, mice in the TAE group were subjected to 10-week aerobic exercise. Carotid pressure and cardiac function were examined before mice were executed by Millar catheter and ultrasound, respectively. Muscle mass of gastrocnemius was weighed; cross-sectional area and the number of capillaries of gastrocnemius were detected by HE and immunohistochemistry, respectively. The mRNA and protein levels of VEGF in skeletal muscle were determined by RT-PCR and western blot, respectively.ResultsWe found that ① 10-week aerobic exercise counteracted hypertension and attenuated cardiac dysfunction in TAC-induced hypertensive mice; ② TAC decreased muscle mass of gastrocnemius and resulted in muscle atrophy, while 10-week aerobic exercise could reserve transverse aortic constriction-induced the decline of muscle mass and muscle atrophy; and ③ TAC reduced the number of capillaries and the protein level of VEGF in gastrocnemius, whereas 10-week aerobic exercise augmented the number of capillaries, the mRNA and protein levels of VEGF in mice were subjected to TAC surgery.ConclusionsThis study indicates that 10-week aerobic exercise might fulfill its blood pressure-lowering effect via improving skeletal muscle microcirculation and increasing muscle mass.

Project description:In the context of most induced pluripotent stem (iPS) cell reprogramming methods, heterogeneous populations of nonproductive and staggered productive intermediates arise at different reprogramming time points1-11. Despite recent reports claiming substantially increased reprogramming efficiencies using genetically modified donor cells12,13 prospectively isolating distinct reprogramming intermediates remains an important goal to decipher reprogramming mechanisms. Previous attempts to identify surface markers of intermediate cell populations were based on the assumption that during reprogramming the cells progressively lose donor cell identity and gradually acquire iPS cell properties1,2,7,8,10. Here, we report that iPS cell and epithelial markers, such as SSEA1 and EpCAM, respectively, are not predictive of reprogramming during early phases. Instead, in a systematic functional surface marker screen we find that early reprogramming-prone cells express a unique set of surface markers, including CD73, CD49d and CD200 that are absent in fibroblasts and iPS cells. Single cell mass cytometry and prospective isolation show that these distinct intermediates are transient and bridge the gap between donor cell silencing and pluripotency marker acquisition during the early, presumably stochastic reprogramming phase2. Expression profiling revealed that the transcriptional regulators Nr0b1 and Etv5 are specifically expressed in this early reprogramming state, preceding activation of key pluripotency regulators such as Rex1, Dppa2, Nanog and Sox2. Both factors are required for the generation of the early intermediate state and fully reprogrammed iPS cells, and thus mark some of the earliest known regulators of iPS cell induction. Our study shows an ordered sequence of transitions during the earliest steps of iPS cell reprogramming that deconvolutes the first steps in a hierarchical series of events that lead to pluripotency acquisition. Samples for poised (CD73+ or CD49d+) and non-poised (CD73-) reprogramming samples were FACS sorted 6 and 9 days after induction of Klf4, Oct4, Sox2 and cMyc in Rosa-rtTA +/- mouse embryonic fibroblasts (MEFs). 'Total' populations are expression analyses for unsorted populations analyzed at the same time points. Control populations were also sampled: mouse embryonic fibroblasts (MEFs), partially reprogrammed cells (SC4) and mouse embryonic stem cell (ESC).

Dataset Information

Skeletal Muscle Subpopulation Rearrangements upon Rhabdomyosarcoma Development through Single-Cell Mass Cytometry.

Publications

Skeletal Muscle Subpopulation Rearrangements upon Rhabdomyosarcoma Development through Single-Cell Mass Cytometry.

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