Regeneration and Long-Term Stability of a Low-Power Eco-Friendly Temperature Sensor Based on a Hydrogel Nanocomposite.

A water-processable and low-cost nanocomposite material, based on gelatin and graphene, has been used to fabricate an environmentally friendly temperature sensor. Demonstrating a temperature-dependent open-circuit voltage between 260 and 310 K, the sensor effectively detects subzero ice formation. Notably, it maintains a constant temperature sensitivity of approximately -19 mV/K over two years, showcasing long-term stability. Experimental evidence demonstrates the efficient regeneration of aged sensors by injecting a few drops of water at a temperature higher than the gelation point of the hydrogel nanocomposite. The real-time monitoring of the electrical characteristics during the hydration reveals the initiation of the regeneration process at the gelation point (~306 K), resulting in a more conductive nanocomposite. These findings, together with a fast response and low power consumption in the range of microwatts, underscore the potential of the eco-friendly sensor for diverse practical applications in temperature monitoring and environmental sensing. Furthermore, the successful regeneration process significantly enhances its sustainability and reusability, making a valuable contribution to environmentally conscious technologies.

Epiretinal membrane development after Ex-Press glaucoma filtration device implant: 2-year results of a case control study.

BACKGROUND: The most common retinal complications after glaucoma surgery are choroidal detachment, hypotony maculopathy, malignant glaucoma, vitreous hemorrhage, endophthalmitis and retinal detachment. However, if glaucoma surgery is a risk factor for the ERM development needs to be clarified. This study aims to assess the incidence of epiretinal membrane (ERM) in 2 years of follow-up in patients with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. METHODS: A prospective, consecutive, single-center, case-control study. We enrolled patients affected by POAG and scheduled for Ex-Press device implant with or without concomitant cataract surgery. The control group was the contralateral eyes which continues anti-glaucomatous eyedrops. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography were performed before surgery, at 6 months and 24 months of follow-up. RESULTS: Eighty-two eyes of 41 consecutive patients, 18 males and 23 females with a mean age of 70, 29 ± 8,45, were analyzed at 24 months. 39.1% of eyes developed ERM: 29.3% were cellophane macular reflex (CMR) and 9.8% were pre-macular fibrosis (PMF). In the control group, 19.5% of eyes developed ERM: 17.1% were CMR and 2.4% were PMF. No statistically significant difference was reported (p = 0.121) between treated and control group. ERM development did not affect significantly the central foveal thickness (260.13 ± 35.01 µm at baseline, 265.03 ± 34.90 µm at 6 months and 275.18 ± 33.31 µm at 24 months) and macular volume (7.75 ± 0.43 mm3 at baseline, 7.77 ± 0.48 mm3 at 6 months and 7.77 ± 0.46 mm3 at 24 months), remained comparable to reported average measures in healthy individuals during the follow-up. Concomitant cataract surgery did not increase the ERM incidence. CONCLUSION: Ex-Press implant may increase the ERM incidence regardless concomitant cataract surgery, accelerating or inducing a posterior vitreous detachment, such as other ocular surgical procedure. Nevertheless, the vast majority of ERM are CMR, not affecting the macular profile.

Inhibition of exosome biogenesis affects cell motility in heterogeneous sub-populations of paediatric-type diffuse high-grade gliomas.

BACKGROUND: Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated the role of exosomes as a route for inter-clonal communication mediating PDHGG migration and invasion. RESULTS: A comprehensive characterisation of seven optical barcoded single-cell-derived clones obtained from two patient-derived cell lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms of genetic and transcriptional profiles between clones as well as marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis of 3D migration and invasion assays showed that the single-cell-derived clones display a higher speed and longer travelled distance when in co-culture compared to mono-culture conditions. To determine the role of exosomes in PDHGG inter-clonal cross-talks, we isolated exosomes released by different clones and characterised them in terms of marker expression, size and concentration. We demonstrated that exosomes are actively internalized by the cells and that the inhibition of their biogenesis, using the phospholipase inhibitor GW4689, significantly reduced the cell motility in mono-culture and more prominently when the cells from the clones were in co-culture. Analysis of the exosomal miRNAs, performed with a miRNome PCR panel, identified clone-specific miRNAs and a set of miRNA target genes involved in the regulation of cell motility/invasion/migration. These genes were found differentially expressed in co-culture versus mono-culture conditions and their expression levels were significantly modulated upon inhibition of exosome biogenesis. CONCLUSIONS: In conclusion, our study highlights for the first time a key role for exosomes in the inter-clonal communication in PDHGG and suggests that interfering with the exosome biogenesis pathway may be a valuable strategy to inhibit cell motility and dissemination for these specific diseases.

Exploring the landscape of tools and resources for the analysis of long non-coding RNAs.

In recent years, research on long non-coding RNAs (lncRNAs) has gained considerable attention due to the increasing number of newly identified transcripts. Several characteristics make their functional evaluation challenging, which called for the urgent need to combine molecular biology with other disciplines, including bioinformatics. Indeed, the recent development of computational pipelines and resources has greatly facilitated both the discovery and the mechanisms of action of lncRNAs. In this review, we present a curated collection of the most recent computational resources, which have been categorized into distinct groups: databases and annotation, identification and classification, interaction prediction, and structure prediction. As the repertoire of lncRNAs and their analysis tools continues to expand over the years, standardizing the computational pipelines and improving the existing annotation of lncRNAs will be crucial to facilitate functional genomics studies.

A New Insight into MYC Action: Control of RNA Polymerase II Methylation and Transcription Termination.

MYC oncoprotein deregulation is a common catastrophic event in human cancer and limiting its activity restrains tumor development and maintenance, as clearly shown via Omomyc, an MYC-interfering 90 amino acid mini-protein. MYC is a multifunctional transcription factor that regulates many aspects of transcription by RNA polymerase II (RNAPII), such as transcription activation, pause release, and elongation. MYC directly associates with Protein Arginine Methyltransferase 5 (PRMT5), a protein that methylates a variety of targets, including RNAPII at the arginine residue R1810 (R1810me2s), crucial for proper transcription termination and splicing of transcripts. Therefore, we asked whether MYC controls termination as well, by affecting R1810me2S. We show that MYC overexpression strongly increases R1810me2s, while Omomyc, an MYC shRNA, or a PRMT5 inhibitor and siRNA counteract this phenomenon. Omomyc also impairs Serine 2 phosphorylation in the RNAPII carboxyterminal domain, a modification that sustains transcription elongation. ChIP-seq experiments show that Omomyc replaces MYC and reshapes RNAPII distribution, increasing occupancy at promoter and termination sites. It is unclear how this may affect gene expression. Transcriptomic analysis shows that transcripts pivotal to key signaling pathways are both up- or down-regulated by Omomyc, whereas genes directly controlled by MYC and belonging to a specific signature are strongly down-regulated. Overall, our data point to an MYC/PRMT5/RNAPII axis that controls termination via RNAPII symmetrical dimethylation and contributes to rewiring the expression of genes altered by MYC overexpression in cancer cells. It remains to be clarified which role this may have in tumor development.

Ultrasound Cyclo Plasty in Patients with Open Angle Glaucoma and High Myopia.

PRCIS: Ultrasound cyclo plasty (UCP) using high-intensity focused ultrasound is an effective and safe procedure in lowering intraocular pressure (IOP) in patients with glaucoma, even in those with high myopia. PURPOSE: This study aimed to evaluate the efficacy and safety of UCP in glaucoma patients with high myopia. MATERIALS AND METHODS: In this retrospective, single-center study, we enrolled 36 eyes divided into 2 groups based on axial length: group A (≥26.00 mm) and group B (<26.00 mm). We collected data about visual acuity, Goldmann applanation tonometry, biomicroscopy, and visual field before the procedure and at 1, 7, 30, 60, 90, 180, and 365 days after the procedure. RESULTS: Mean IOP significantly decreased in both groups after treatment ( P <0.001). Mean IOP reduction from baseline to the last visit was 9.8±6.6 mmHg (38.7%) in group A and 9.6±6.3 mmHg (34.8%) in group B ( P <0.001). Mean IOP at the last visit was 15.8±4.1 mmHg in the myopic group and 18.1±5.6 mmHg in the non-myopic one. Regarding the number of IOP-lowering eyedrops being taken by our patients, statistically significant differences were found between groups A and B neither at baseline (2.8±0.9 and 2.6±1.0; P =0.568) nor 1 year after the procedure (2.5±1.1 and 2.6±1.1; P =0.762). No major complications occurred. All minor adverse events resolved within a few days. CONCLUSION: UCP seems to be an effective and well-tolerated strategy to lower IOP in glaucoma patients with high myopia.

Crosstalk between cilia and autophagy: implication for human diseases.

Macroautophagy/autophagy is a self-degradative process necessary for cells to maintain their energy balance during development and in response to nutrient deprivation. Autophagic processes are tightly regulated and have been found to be dysfunctional in several pathologies. Increasing experimental evidence points to the existence of an interplay between autophagy and cilia. Cilia are microtubule-based organelles protruding from the cell surface of mammalian cells that perform a variety of motile and sensory functions and, when dysfunctional, result in disorders known as ciliopathies. Indeed, selective autophagic degradation of ciliary proteins has been shown to control ciliogenesis and, conversely, cilia have been reported to control autophagy. Moreover, a growing number of players such as lysosomal and mitochondrial proteins are emerging as actors of the cilia-autophagy interplay. However, some of the published data on the cilia-autophagy axis are contradictory and indicate that we are just starting to understand the underlying molecular mechanisms. In this review, the current knowledge about this axis and challenges are discussed, as well as the implication for ciliopathies and autophagy-associated disorders.

Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry.

Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying distinctive molecular alterations and clinical outcomes (inter-tumor heterogeneity). Moreover, deep cellular and molecular profiling studies highlighted the coexistence of genetically and phenotypically different subpopulations within the same tumor mass (intra-tumor heterogeneity). Despite the recent advances made in the field, the marked heterogeneity of PDHGGs still impedes the development of effective targeted therapies and the identification of suitable biomarkers. In order to fill the existing gap, we used mass cytometry to dissect PDHGG inter- and intra-heterogeneity. This is one of the most advanced technologies of the "-omics" era that, using antibodies conjugated to heavy metals, allows the simultaneous measurement of more than 40 markers at single-cell level. To this end, we analyzed eight PDHGG patient-derived cell lines from different locational and molecular subgroups. By using a panel of 15 antibodies, directly conjugated to metals or specifically customized to detect important histone variants, significant differences were highlighted in the expression of the considered antigens. The single-cell multiparametric approach realized has deepened our understanding of PDHGG, confirming a high degree of intra- and inter-tumoral heterogeneity and identifying some antigens that could represent useful biomarkers for the specific PDHGG locational or molecular subgroups.

Electrochemical Performance of Biopolymer-Based Hydrogel Electrolyte for Supercapacitors with Eco-Friendly Binders.

An environmentally friendly hydrogel based on gelatin has been investigated as a gel polymer electrolyte in a symmetric carbon-based supercapacitor. To guarantee the complete sustainability of the devices, biomaterials from renewable resources (such as chitosan, casein and carboxymethyl cellulose) and activated carbon (from coconut shells) have been used as a binder and filler within the electrode, respectively. The electrochemical properties of the devices have been compared by using cyclic voltammetry, galvanostatic charge/discharge curves and impedance spectroscopy. Compared to the liquid electrolyte, the hydrogel supercapacitors show similar energy performance with an enhancement of stability up to 12,000 cycles (e.g., chitosan as a binder). The most performant device can deliver ca. 5.2 Wh/kg of energy at a high power density of 1256 W/kg. A correlation between the electrochemical performances and charge storage mechanisms (involving faradaic and non-faradaic processes) at the interface electrode/hydrogel has been discussed.

Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.

Selective degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is initiated by ER-phagy receptors, which facilitate the incorporation of ER fragments into autophagosomes. FAM134 reticulon family proteins (FAM134A, FAM134B, and FAM134C) are ER-phagy receptors with structural similarities and nonredundant functions. Whether they respond differentially to the stimulation of ER-phagy is unknown. Here, we describe an activation mechanism unique to FAM134C during starvation. In fed conditions, FAM134C is phosphorylated by casein kinase 2 (CK2) at critical residues flanking the LIR domain. Phosphorylation of these residues negatively affects binding affinity to the autophagy proteins LC3. During starvation, mTORC1 inhibition limits FAM134C phosphorylation by CK2, hence promoting receptor activation and ER-phagy. Using a novel tool to study ER-phagy in vivo and FAM134C knockout mice, we demonstrated the physiological relevance of FAM134C phosphorylation during starvation-induced ER-phagy in liver lipid metabolism. These data provide a mechanistic insight into ER-phagy regulation and an example of autophagy selectivity during starvation.

MAPK15 protects from oxidative stress-dependent cellular senescence by inducing the mitophagic process.

Mitochondria are the major source of reactive oxygen species (ROS), whose aberrant production by dysfunctional mitochondria leads to oxidative stress, thus contributing to aging as well as neurodegenerative disorders and cancer. Cells efficiently eliminate damaged mitochondria through a selective type of autophagy, named mitophagy. Here, we demonstrate the involvement of the atypical MAP kinase family member MAPK15 in cellular senescence, by preserving mitochondrial quality, thanks to its ability to control mitophagy and, therefore, prevent oxidative stress. We indeed demonstrate that reduced MAPK15 expression strongly decreases mitochondrial respiration and ATP production, while increasing mitochondrial ROS levels. We show that MAPK15 controls the mitophagic process by stimulating ULK1-dependent PRKN Ser108 phosphorylation and inducing the recruitment of damaged mitochondria to autophagosomal and lysosomal compartments, thus leading to a reduction of their mass, but also by participating in the reorganization of the mitochondrial network that usually anticipates their disposal. Consequently, MAPK15-dependent mitophagy protects cells from accumulating nuclear DNA damage due to mitochondrial ROS and, consequently, from senescence deriving from this chronic DNA insult. Indeed, we ultimately demonstrate that MAPK15 protects primary human airway epithelial cells from senescence, establishing a new specific role for MAPK15 in controlling mitochondrial fitness by efficient disposal of old and damaged organelles and suggesting this kinase as a new potential therapeutic target in diverse age-associated human diseases.

Health status and the Great Recession. Evidence from electronic health records.

We investigate the impact of the Great Recession in Italy on the incidence of chronic diseases using new individual longitudinal data from Electronic Health Records. We exploit the exogenous shock in the economic conditions occurred in 2008 to estimate heterogeneous effects of an unprecedented rise in local unemployment rates in an individual fixed-effects model. Our results document that harsh economic downturns have a negative long-lasting effect on cardiovascular disease and a temporary effect on depression. This effect is heterogeneous across gender, increases with age and is stronger right before the retirement age. An important policy recommendation emerging from this study is that prolonged economic downturns constitute an additional external risk for individual health and not a temporary benefit.

Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue.

Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program. When re-uptaken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-γ signaling and the levels of mitochondrial proteins, including UCP1. Their removal via the phagocytic activity of BAT-resident macrophages is instrumental in preserving BAT physiology. Depletion of macrophages in vivo causes the abnormal accumulation of extracellular mitochondrial vesicles in BAT, impairing the thermogenic response to cold exposure. These findings reveal a homeostatic role of tissue-resident macrophages in the mitochondrial quality control of BAT.

Prenatal air pollution exposure and neonatal health.

Air pollution has been shown to have adverse effects on many health outcomes including respiratory effects, cardiovascular effects, and mortality. However, evidence on the effects of prenatal exposure is still limited. We investigate the causal impact of prenatal exposure to air pollution on neonatal health in Italy in the 2000s. We exploit variation in rainfall shocks to instrument for non-random air pollution exposure. Our empirical setting combines detailed information on mother's residential location from birth certificates with PM10 concentrations from air pollution monitors. Ten additional units in the average PM10 level (approximately one standard deviation) would decrease birth weight by about 0.5% and gestational age by 0.16%; it would increase the prevalence of low birth weight by 22% and of preterm birth by 16%. The effects are stronger in magnitude for third trimester exposure and for less educated mothers. These findings suggest that the health impacts of air pollution on newborns are unequally distributed in the population.

An Update on Circular RNA in Pediatric Cancers.

Circular RNAs (circRNAs) are a class of single-stranded closed noncoding RNA molecules which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, only recently there appeared an increased interest in the understanding of their regulatory importance. Among their most relevant characteristics are high stability, abundance and evolutionary conservation among species. CircRNAs are implicated in several cellular functions, ranging from miRNA and protein sponges to transcriptional modulation and splicing. Additionally, circRNAs' aberrant expression in pathological conditions is bringing to light their possible use as diagnostic and prognostic biomarkers. Their use as indicator molecules of pathological changes is also supported by their peculiar covalent closed cyclic structure which bestows resistance to RNases. Their regulatory role in cancer pathogenesis and metastasis is supported by studies involving human tumors that have investigated different expression profiles of these molecules. As endogenous competitive RNA, circRNAs can regulate tumor proliferation and invasion and they arouse great consideration as potential therapeutic biomarkers and targets for cancer. In this review, we describe the most recent findings on circRNAs in the most common pediatric solid cancers (such as brain tumors, neuroblastomas, and sarcomas) and in more rare ones (such as Wilms tumors, hepatoblastomas, and retinoblastomas).

When particulate matter strikes cities: Social disparities and health costs of air pollution.

We investigate the heterogeneous effects of particle pollution on Italian daily hospitalizations and their costs by exploiting public transportation strikes as plausibly-exogenous shocks in pollution exposure. We find that a one standard deviation increase in PM10 causes additional 0.79 hospitalizations per 100,000 residents, and the effect is stronger for the elderly, low educated individuals and migrants. Furthermore, we find that young individuals, an arguably healthy age group, exhibit economically meaningful responses to air pollution with an effect ranging between 0.45 and 1.04. Our results imply a large role of avoidance behavior driving heterogeneous marginal health effects. Total daily costs of a one standard deviation increase in PM10 represent 0.5% of the total daily health expenditure, and 85% of this additional spending comes from more patients hospitalized, while the remaining 15% can be attributable to more costly, and likely more complex, hospitalizations.

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

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-KrasG12D/+;Tp53Fl/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.

Single-Cell Gene Network Analysis and Transcriptional Landscape of MYCN-Amplified Neuroblastoma Cell Lines.

Neuroblastoma (NBL) is a pediatric cancer responsible for more than 15% of cancer deaths in children, with 800 new cases each year in the United States alone. Genomic amplification of the MYC oncogene family member MYCN characterizes a subset of high-risk pediatric neuroblastomas. Several cellular models have been implemented to study this disease over the years. Two of these, SK-N-BE-2-C (BE2C) and Kelly, are amongst the most used worldwide as models of MYCN-Amplified human NBL. Here, we provide a transcriptome-wide quantitative measurement of gene expression and transcriptional network activity in BE2C and Kelly cell lines at an unprecedented single-cell resolution. We obtained 1105 Kelly and 962 BE2C unsynchronized cells, with an average number of mapped reads/cell of roughly 38,000. The single-cell data recapitulate gene expression signatures previously generated from bulk RNA-Seq. We highlight low variance for commonly used housekeeping genes between different cells (ACTB, B2M and GAPDH), while showing higher than expected variance for metallothionein transcripts in Kelly cells. The high number of samples, despite the relatively low read coverage of single cells, allowed for robust pathway enrichment analysis and master regulator analysis (MRA), both of which highlight the more mesenchymal nature of BE2C cells as compared to Kelly cells, and the upregulation of TWIST1 and DNAJC1 transcriptional networks. We further defined master regulators at the single cell level and showed that MYCN is not constantly active or expressed within Kelly and BE2C cells, independently of cell cycle phase. The dataset, alongside a detailed and commented programming protocol to analyze it, is fully shared and reusable.

Integrating Patient-Specific Information into Logic Models of Complex Diseases: Application to Acute Myeloid Leukemia.

High throughput technologies such as deep sequencing and proteomics are increasingly becoming mainstream in clinical practice and support diagnosis and patient stratification. Developing computational models that recapitulate cell physiology and its perturbations in disease is a required step to help with the interpretation of results of high content experiments and to devise personalized treatments. As complete cell-models are difficult to achieve, given limited experimental information and insurmountable computational problems, approximate approaches should be considered. We present here a general approach to modeling complex diseases by embedding patient-specific genomics data into actionable logic models that take into account prior knowledge. We apply the strategy to acute myeloid leukemia (AML) and assemble a network of logical relationships linking most of the genes that are found frequently mutated in AML patients. We derive Boolean models from this network and we show that by priming the model with genomic data we can infer relevant patient-specific clinical features. Here we propose that the integration of literature-derived causal networks with patient-specific data should be explored to help bedside decisions.

SCA-1 micro-heterogeneity in the fate decision of dystrophic fibro/adipogenic progenitors.

The term micro-heterogeneity refers to non-genetic cell to cell variability observed in a bell-shaped distribution of the expression of a trait within a population. The contribution of micro-heterogeneity to physiology and pathology remains largely uncharacterised. To address such an issue, we investigated the impact of heterogeneity in skeletal muscle fibro/adipogenic progenitors (FAPs) isolated from an animal model of Duchenne muscular dystrophy (DMD), the mdx mouse. FAPs play an essential role in muscle homoeostasis. However, in pathological conditions or ageing, they are the source of intramuscular infiltrations of fibrotic or adipose tissue. By applying a multiplex flow cytometry assay, we characterised and purified from mdx muscles two FAP cell states expressing different levels of SCA-1. The two cell states are morphologically identical and repopulate each other after several growth cycles. However, they differ in their in vitro behaviour. Cells expressing higher levels of SCA-1 (SCA1-High-FAPs) differentiate more readily into adipocytes while, when exposed to a fibrogenic stimulation, increase the expression of Col1a1 and Timp1 mRNA. A transcriptomic analysis confirmed the adipogenic propensity of SCA1-High-FAPs. In addition, SCA1-High-FAPs proliferate more extensively ex vivo and display more proliferating cells in dystrophic muscles in comparison to SCA1-Low-FAPs. Adipogenesis of both FAP cell states is inhibited in vitro by leucocytes from young dystrophic mice, while leucocytes isolated from aged dystrophic mice are less effective in limiting the adipogenesis of SCA1-High-FAPs suggesting a differential regulatory effect of the microenvironment on micro-heterogeneity. Our data suggest that FAP micro-heterogeneity is modulated in pathological conditions and that this heterogeneity in turn may impact on the behaviour of interstitial mesenchymal cells in genetic diseases.