HNF1A-MODY is a subtype of monogenic diabetes caused by mutations in the hepatocyte nuclear factor-1 homeobox A (HNF1A) gene. While the role of HNF1A in pancreatic beta cells has been extensively studied, its role in other cell types, such as endothelial cells (ECs), is less understood. Despite the pharmacologically controlled glycemia in HNF1A-MODY patients, still cardiovascular disorders and other endothelial dysfunction diseases, such as retinopathy, are quite common. Therefore, the aim of the current study was to look for potential molecular alterations in the ECs related to HNF1A-MODY disease. To understand the molecular pathways underlying this effect, ECs from three sets of human pluripotent stem cells (hiPSC-ECs) were used – two isogenic and one patient set. The patient set consisted of four hiPSCs lines with two healthy/control lines and two hiPSCs lines derived from HNF1A-MODY patients. The control isogenic set has a control (healthy) and two CRISPR/Cas9-mutated hiPSCs lines, with monoallelic or biallelic mutations in the HNF1A. The patient isogenic set consists of HNF1A-MODY patient hiPSCs line and two repaired (control) lines. All these lines were subsequently differentiated toward ECs (hiPSC-ECs) and used for global transcriptome, global proteome, and other functional analyses. Additionally, selected results were confirmed in primary ECs, where HNF1A expression was silenced. The integrated global transcriptome and proteome analyses of the control isogenic set (mutated versus unmutated), show differences in actin-based cytoskeleton, general metabolism, and proteoglycan-related genes. All HNF1A-mutated hiPSC-ECs had shorter glycocalyx layer in comparison to their control counterparts. The same phenotype can be mimicked by silencing the HNF1A in primary ECs. Additionally, HNF1A-mutated control isogenic lines showed increased migratory potential, which aligns with a decrease in the actin stress fibres. Similarly, increased migration is observed after HNF1A silencing in patient-specific hiPSC-ECs or in primary ECs. Taken together, these results reveal for the first time that mutations in the HNF1A cause proteomic and transcriptomic changes in ECs that affect their function through reduction of the glycocalyx layer and changes in the cell migration. Cumulatively, these changes could account for signs of endothelial dysfunction in HNF1A-MODY patients.

Abstract Aims While the muscle-enriched microRNA-378a (miR-378a) has been implicated in cardiac hypertrophy and stress responses, its role in maintaining cardiomyocyte metabolic homeostasis, mitochondrial function, and angiogenic paracrine signaling under physiological and post-injury conditions remains unclear. This study addresses these gaps by examining the molecular and functional consequences of miR-378a deficiency in murine heart and human cardiomyocytes. Methods and Results Cardiac structure and function were analyzed in miR-378a-deficient (miR-378a−/−) and wild-type (miR-378a+/+) mice at 12 weeks and 17 months of age, revealing that miR-378a loss promoted myocardial fibrosis, altered IGF1R–AKT signaling, and impaired cardiac performance, with age-dependent effects. Integrated transcriptomic and proteomic analyses in miR-378a-/- and control mice, as well as in human iPSC-derived cardiomyocytes (hiPSC-CM) of both genotypes, revealed deregulated pathways related to translation, metabolism, and cardiomyopathy-associated signaling. In hiPSC-CM, miR-378a knockout (KO) impaired mitochondrial respiration, disrupted mitochondrial morphology, and reduced mitochondrial DNA content, accompanied by altered mitophagy and biogenesis. KO cells also showed increased glucose uptake but reduced glycogen storage, accompanied by changes in key metabolic regulators, and displayed diminished angiogenic potential. Finally, hiPSC-CM overexpressing miR-378a were delivered in a mouse model of acute myocardial infarction, but overexpression did not further enhance their therapeutic effect. Conclusions This study broadens our understanding of miR-378a’s physiological role in murine hearts and human cardiomyocytes, demonstrating its impact on contractility, mitochondrial integrity, glucose metabolism, and angiogenic paracrine signaling. However, overexpression of miR-378a in hiPSC-CM offers limited additional benefit in cell therapy for acute myocardial infarction.

Becker Muscular Dystrophy (BMD) is caused by in-frame mutations in the DMD gene, leading to the production of internally truncated but partially functional dystrophin. Although cardiac involvement is a major contributor to disease burden in BMD, the cellular mechanisms driving cardiomyopathy remain incompletely understood. While emerging evidence suggests that iron imbalance may contribute to oxidative stress and mitochondrial dysfunction in muscular dystrophies, its role in BMD-associated cardiomyopathy has not been defined. Building on our previous findings of dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes from Duchenne muscular dystrophy (DMD), we investigated whether similar alterations are present in BMD using patient-specific and genome-corrected hiPSC-CM models. HiPSC lines derived from two BMD patients and their CRISPR/Cas9-corrected isogenic controls displayed normal karyotype, pluripotency, and efficient differentiation into cardiomyocytes (hiPSC-CMs). BMD hiPSC-CMs showed elevated ROS levels and decreased cytoplasmic and mitochondrial labile iron pools, accompanied by reduced expression of mitoNEET (CISD1), a regulator of mitochondrial iron handling. We also detected changes in the expression of genes involved in iron storage (FTH1), uptake (TFRC), and export (SLC40A1), suggesting a dysregulation of iron trafficking. Importantly, correction of DMD mutation by CRISPR/Cas9 gene editing reversed the effects observed in BMD cardiomyocytes. These results extend our previous observations in DMD to BMD cardiomyocytes and suggest that full-length dystrophin is essential for maintaining cardiac iron homeostasis.

Melanogenesis is a defining feature of melanocyte biology and influences melanoma pathogenesis; however, tumor-specific regulators of this process remain incompletely understood. Here, we investigate how heme oxygenase-1 (HO-1) regulates pigmentation in malignant and homeostatic contexts. Using B16-F10 melanoma cells engineered to express varying levels of HO-1, we show that HO-1 abundance correlates with pigmentation intensity and tyrosinase activity, without affecting transcription of core melanogenesis genes. Under pigment-inducing conditions, HO-1 inversely regulates intracellular melanin retention and pigment export, with inhibition of melanosome transfer confirming a role for HO-1 in melanosome trafficking and secretion. Co-culture experiments reveal that stromal HO-1 promotes melanoma pigmentation through paracrine effects on tyrosinase expression. Transcriptomic analyses of human melanoma datasets show that HMOX1 expression correlates with pathways related to melanosome acidification, copper homeostasis, and lysosomal transport rather than classical melanogenic programs. In contrast, HO-1 is dispensable in the non-malignant melanocytic conditions tested here-murine iPSC-derived melanocytes during differentiation and Melan-A melanocytes. Together, these findings identify HO-1 as a context-dependent regulator of melanoma pigmentation and a potential selective target for modulating pigmentation-dependent tumor traits.

Lymphedema-distichiasis syndrome (LDS) is an autosomal dominant genetic disorder associated with mutations in forkhead box C2 (FOXC2) gene, critical for lymphatic endothelial cell (LEC) differentiation. LDS patients suffer from swelling of limbs (lymphedema) due to excessive lymph accumulation and are characterized by the presence of additional row of eyelashes (distichiasis). Here, we generated human induced pluripotent stem cells (hiPSCs) from LDS patient-derived peripheral blood mononuclear cells (PBMCs). LDS hiPSC line allows in vitro modeling and investigation of the molecular mechanisms of LDS upon differentiation towards LEC.

Homozygous deletions of methylthioadenosine phosphorylase (MTAP), located on chromosome 9p21 are observed in 10 to 15% of all human tumors. This deletion leads to a substantial methylthioadenosine (MTA) build-up within cells. At high concentrations, MTA acts as a highly selective inhibitor of the PRMT5 methyltransferase, specifically competing with its substrate, S-adenosylmethionine (SAM). Hence, selectively targeting of residual PRMT5 levels, which are essential for survival of cancers, represents a promising strategy for eliminating cancer cells with homozygous MTAP deletion. There is growing evidence that MTA accumulation enhances immunosuppressive tumor microenvironment. Moreover, tumor-specific PRMT5 inhibition has been shown to enhance antitumor immune responses, opening the possibility of combining MTAP-deletion specific MTA-cooperative PRMT5 inhibitors with cancer immunotherapy. Ryvu has developed RVU305, a potentially best-in-class MTA-cooperative PRMT5 inhibitor, characterized by favorable drug-like physicochemical properties, low nanomolar potency, and differential efficacy in MTAP-null cancer cells. To evaluate the immunomodulatory activity of RVU305, we developed an MC38 syngeneic colon cancer model with homozygous deletion of MTAP and CDKN2A genes. The tumor growth inhibitory activity of RVU305 was assessed following oral administration, both alone and in combination with anti-PD-1 antibody. Effects on tumor-infiltrating lymphocytes were analyzed using flow cytometry. Changes in IFN-γ-secreting T cells were evaluated using ELISpot. PRMT5 inhibition in MTAP-null cancer cells, as well as in stromal and infiltrating lymphocytes, was assessed via SDMA IHC staining. RVU305 demonstrated robust tumor growth inhibition (TGI) in MC38 tumors with MTAP loss, with confirmed target engagement, while the growth of the MC38 variant with an intact MTAP gene was unaffected at pharmacologically active doses. Furthermore, co-treatment with RVU305 and anti-PD-1 antibody was well tolerated and resulted in antitumor activity. Immunomodulatory effects of RVU305, both alone and in combination with anti-PD-1, were supported by pharmacodynamic changes observed in tumor tissue. Taken together, these studies confirm that MTA-cooperative PRMT5 inhibitors induce a strong synthetic lethal phenotype in MTAP-deleted cancers, offering an exciting therapeutic opportunity for a large patient population and potentially addressing an unmet clinical need when combined with immunotherapy. Anna Bartosik, Adam Radzimierski, Aneta Bobowska, Aleksandra Więckowska, Kamil Kuś, Jacek Faber, Bożena Winnik, Agata Stachowicz-Wałaszek, Agnieszka Ludwig-Słomczyńska, Kamila Kozłowska-Tomczyk, Marta Wadowska, Szymon Woroszyło, Mateusz Stoszko, Aniela Gołas, Paulina Podkalicka, Adrian Zarębski, Agnieszka Piątek, Maciej Kujawa, Beata Kowalska, Julia Wirkijowska, Stefan Chmielewski, Jacek Stępniewski, Mateusz Ogórek, Lika Osugui, Agnieszka Szymula, Agnieszka Dorman, Kamila Białkowska, Marcelina Chmiel, Milena Mazan, Tomasz Rzymski, Karolina Gluza, Joanna Krawczyk, Marcin Kowiel, Adam Marciniak, Michał Combik, Oleksii Bryzghalov, Mateusz Nowak, Didier Pez, Krzysztof Brzózka. Preclinical candidate RVU305, an MTA-cooperative PRMT5 inhibitor, shows activity in MTAP-deleted tumors resistant to immune checkpoint treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4231.

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease caused by mutations in the DMD gene, leading to the absence or dysfunction of dystrophin. While cardiac and skeletal muscles are both affected, tissue-specific differences in disease manifestation and dystrophin regulation remain poorly understood. Methods: To investigate these differences, we established a human induced pluripotent stem cell (hiPSC) model of DMD from peripheral blood mononuclear cells (PBMC) of a patient carrying a splice-site mutation in intron 68 (c.9975-1G>T). An isogenic control line was generated via CRISPR/Cas9 correction. Both repaired and DMD hiPSCs were differentiated into cardiomyocytes (hiPSC-CMs) and skeletal muscle cells (hiPSC-SMs). Transcript and protein analyses were performed, along with functional assessment using microelectrode array. Results: Transcript analysis revealed an in-frame deletion of two amino acids (Tyr3325 and Arg3326) due to skipping of the first six nucleotides of exon 69. Despite this, near full-length Dp427 was detected by western blot, along with expression of Dp116 in hiPSC-CMs. Dystrophin levels were preserved in DMD hiPSC-CMs but markedly reduced in hiPSC-SMs, suggesting tissue-specific regulation. Functional analysis showed altered ?-adrenergic responsiveness in DMD hiPSC-CMs, with increased beating frequency and accelerated repolarization upon isoproterenol stimulation. Conclusions: Our study identifies a splice-site mutation that preserves high level of dystrophin expression in cardiac but reduced in skeletal muscle and reveals Dp116 expression in cardiomyocytes. These findings highlight the importance of tissue context in DMD and demonstrate the power of hiPSC-based systems for dissecting mutation-specific effects. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work was supported by the Polish National Science Centre (NCN) grant MAESTRO [2018/30/A/NZ3/00412] to J.D. The multi-electrode array (MEA) system used for electrophysiological analyses was purchased with funds from the Polish National Science Centre (NCN) grant SHENG-2 [2021/40/Q/NZ3/00165] to J.D. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Bioethical Committee of the Warsaw Medical University (approval no. KB/111/2019, approved on 10.06.2019; project title: Molecular mechanisms of heart failure in Duchenne and Becker muscular dystrophy). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are included in the article and its supplementary materials.

The extracellular matrix protein laminin-α2 is essential for preserving the integrity of skeletal muscle fibers during contraction. Its importance is reflected by the severe, congenital LAMA2-related muscular dystrophy (LAMA2 MD) caused by loss-of-function mutations in the LAMA2 gene. While laminin-α2 has an established role in structurally supporting muscle fibers, it remains unclear whether it exerts additional functions that contribute to the maintenance of skeletal muscle integrity. Here, we report that in healthy muscle, activated muscle stem cells (MuSCs) express Lama2 and remodel their microenvironment with laminin-α2. By characterizing LAMA2 MD-afflicted MuSCs and generating MuSC-specific Lama2 knockouts, we show that MuSC-derived laminin-α2 is essential for rapid MuSC expansion and regeneration. In humans, we identify LAMA2 expression in MuSCs and demonstrate that loss-of-function mutations impair cell-cycle progression of myogenic precursors. In summary, we show that self-secreted laminin-α2 supports MuSC proliferation post-injury, thus implicating MuSC dysfunction in LAMA2 MD pathology.

Abstract Background Adult muscle-resident myogenic stem cells, satellite cells (SCs), that play non-redundant role in muscle regeneration, are intrinsically impaired in Duchenne muscular dystrophy (DMD). Previously we revealed that dystrophic SCs express low level of anti-inflammatory and anti-oxidative heme oxygenase-1 (HO-1, HMOX1). Here we assess whether targeted induction of HMOX1 affect SC function and alleviates hallmark symptoms of DMD. Methods We generated double-transgenic mouse model (mdx;HMOX1Pax7Ind) that allows tamoxifen (TX)-inducible HMOX1 expression in Pax7 positive cells of dystrophic muscles. Mdx;HMOX1Pax7Ind and control mdx mice were subjected to 5-day TX injections (75 mg/kg b.w.) followed by acute exercise protocol with high-speed treadmill (12 m/min, 45 min) and downhill running to worsen skeletal muscle phenotype and reveal immediate effects of HO-1 on muscle pathology and SC function. Results HMOX1 induction caused a drop in SC pool in mdx;HMOX1Pax7Ind mice (vs. mdx counterparts), while not exaggerating the effect of physical exercise. Upon physical exercise, the proliferation of SCs and activated CD34− SC subpopulation, was impaired in mdx mice, an effect that was reversed in mdx;HMOX1Pax7Ind mice, however, both in vehicle- and TX-treated animals. This corresponded to the pattern of HO-1 expression in skeletal muscles. At the tissue level, necrotic events of selective skeletal muscles of mdx mice and associated increase in circulating levels of muscle damage markers were blunted in HO-1 transgenic animals which showed also anti-inflammatory cytokine profile (vs. mdx). Conclusions Targeted expression of HMOX1 plays protective role in DMD and alleviates dystrophic muscle pathology.

Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by in-frame deletions in the dystrophin gene (DMD), leading to progressive muscle degeneration and weakness. We generated a human induced pluripotent stem cell (hiPSC) line from a BMD patient. BMD hiPSCs were then engineered by CRISPR/Cas9-mediated knock-in of missing exons 3–9 of DMD gene. Obtained hiPSC line may be a valuable tool for investigating the mechanisms underlying BMD pathogenesis.

Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by mutations in the dystrophin gene. Cardiomyopathy is the leading cause of death in DMD patients, but the exact mechanisms underlying it remain unclear. Due to the limitations of animal models, patient-derived human models need to be developed to investigate cardiac pathophysiological mechanisms better. Hence, 3D human cardiac organoids (hCOs) are designed to more closely resemble the structural and functional properties of the human heart than traditional 2D cell cultures or animal models. For this purpose, we generated DMD patient-derived induced pluripotent stem cells (hiPSC) and corrected DMD mutation with CRISPR/Cas9 gene editing, establishing isogenic control lines. Healthy controls and CRISPR/Cas9 edited cells with introduced DMD gene exon 50 deletion were also sources for these cell types. Under specified culture conditions, these stem cells differentiate into various cardiac cell types, including cardiomyocytes (CM), endothelial cells (EC), and cardiac fibroblasts (CF). We affirmed the presence of specific markers (troponin T for CM, DDR2 for CF, and CD31 and VE-cadherin for EC), indicating successful differentiation. Self-aggregation of CM, CF, and EC at controlled ratios (CM: 75%, CF: 15%, EC: 15%) resulted in the formation of 3D cardiac organoids. Overall, we successfully generated cardiac organoids from hiPSCs derived from DMD patients, healthy donors, and isogenic control samples, which will be used to understand the mechanisms of DMD cardiomyopathy further. Grants support: National Science Centre: MAESTRO 2018/30/A/NZ3/00412.

Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) offer an attractive platform to evaluate the mechanisms of cardiovascular-related incidents and to develop and test new drugs for heart diseases. This work focuses on the comparison of two hiPSC-CM differentiation protocols: the GiWi method based on temporal modulation of the Wnt/β-catenin pathway and the commercially available PSC Cardiomyocyte Differentiation Kit. We underlined the need to optimize several parameters such as cell density or small molecule concentration (CHIR-99021, IWR-1) to obtain functional hiPSC-CMs. Both protocols yield a similar differentiation efficiency; therefore, the choice of a particular procedure may depend on the preferences of the experimenter.

Induced pluripotent stem cell (iPSC) technology offers a promising approach for DMD modeling while preserving the patient's genetic background. This study aimed to generate iPSCs lacking expression of dystrophin isoforms Dp427 and Dp116 from a DMD patient diagnosed with a point mutation in intron 68 (c.9975-1 G>T) and to establish an isogenic line by repairing the mutation with CRISPR/Cas9 gene editing. The iPSCs were obtained by reprogramming of patient's peripheral blood mononuclear cells. Isogenic cell line was generated by correction of mutation using CRISPR/Cas9 editing and repair template and was confirmed by sequencing. iPSCs were then differentiated to cardiomyocytes (iPSC-CMs) and skeletal muscles (iPSC-SMs). Interestingly, sequencing of dystrophin RNA from patient-derived iPSC-CMs, iPSC-SMs and isogenic controls unveiled that the point mutation in intron 68 resulted in the deletion of only the first 6 nucleotides of exon 69, and absence of tyrosine and arginine (3325 and 3326 amino acids) while maintaining the reading frame, as Western blot analysis confirmed truncated dystrophin expression. Moreover, we observed comparable levels of dystrophin protein between repaired and patient-derived iPSC-CMs, contrasting with diminished dystrophin levels in patient iPSC-SMs. The described mutation of 3’ splice site is a rare case that does not lead to total lack of dystrophin expression. The observed discrepancy between protein levels highlights tissue-specific differences in dystrophin regulation. Moreover, the deletion of two amino acids may distort the binding of β-dystroglycan and dystrophin function, which underscores the importance of further research for a comprehensive understanding of Duchenne muscular dystrophy pathophysiology.

Aims Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a serious life-threatening complication, the mechanisms of which have not been fully established, and therefore no effective treatment is currently available. The purpose of the study was to identify new molecular signatures of the cardiomyopathy development in DMD. Methods and results For modelling of DMD-associated cardiomyopathy, we prepared three pairs of isogenic control and dystrophin-deficient human induced pluripotent stem cell (hiPSC) lines. Two isogenic hiPSC lines were obtained by CRISPR/Cas9-mediated deletion of DMD exon 50 in unaffected cells generated from healthy donor and then differentiated into cardiomyocytes (hiPSC-CM). The latter were subjected to global transcriptomic and proteomic analyses followed by more in-depth investigation of selected pathway and pharmacological modulation of observed defects. Proteomic analysis indicated a decrease in the level of mitoNEET protein in dystrophin-deficient hiPSC-CM, suggesting alteration in iron metabolism. Further experiments demonstrated increased labile iron pool both in the cytoplasm and mitochondria, a decrease in ferroportin level and an increase in both ferritin and transferrin receptor in DMD hiPSC-CM. Importantly, CRISPR/Cas9-mediated correction of the mutation in the patient-derived hiPSC reversed the observed changes in iron metabolism and restored normal iron levels in cardiomyocytes. Moreover, treatment of DMD hiPSC-CM with deferoxamine (DFO, iron chelator) or pioglitazone (mitoNEET stabilizing compound) decreased the level of reactive oxygen species in DMD hiPSC-CM. Conclusion To our knowledge, this study demonstrated for the first time impaired iron metabolism in human DMD cardiomyocytes, and potential reversal of this effect by correction of DMD mutation or pharmacological treatment. This implies that iron overload-regulating compounds may serve as novel therapeutic agents in DMD-associated cardiomyopathy.

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease. Although it leads to muscle weakness, affected individuals predominantly die from cardiomyopathy, which remains uncurable. Accumulating evidence suggests that an overexpression of utrophin may counteract some of the pathophysiological outcomes of DMD. The aim of this study was to investigate the role of utrophin in dystrophin-deficient human cardiomyocytes (CMs) and to test whether an overexpression of utrophin, implemented via the CRISPR-deadCas9-VP64 system, can improve their phenotype. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) lacking either dystrophin (DMD) or both dystrophin and utrophin (DMD KO/UTRN(+/-)). We carried out proteome analysis, which revealed considerable differences in the proteins related to muscle contraction, cell-cell adhesion, and extracellular matrix organization. Furthermore, we evaluated the role of utrophin in maintaining the physiological properties of DMD hiPSC-CMs using atomic force microscopy, patch-clamp, and Ca2+ oscillation analysis. Our results showed higher values of afterhyperpolarization and altered patterns of cytosolic Ca2+ oscillations in DMD; the latter was further disturbed in DMD KO/UTRN(+/-) hiPSC-CMs. Utrophin upregulation improved both parameters. Our findings demonstrate for the first time that utrophin maintains the physiological functions of DMD hiPSC-CMs, and that its upregulation can compensate for the loss of dystrophin.

Disease modeling of neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), is hindered by limited accessibility of affected cells. This problem can be overcome by generation of human induced pluripotent stem cells (hiPSC), which can be then differentiated into required cells. Here, we describe the detailed protocol of hiPSC establishment from peripheral blood mononuclear cells (PBMC) of two ALS patients with detected expansion of G4C2 (GGGGCC) repeats in the first intron of C9ORF72 gene, known to be linked with the most common form of familial ALS.Successful PBMC reprogramming with non-integrating Sendai vectors was confirmed by expression of pluripotency markers: OCT4, NANOG, SSEA4, and TRA-1-60 in obtained hiPSC and their ability to differentiate into cells of three germ layers.The generated ALS-patient-specific hiPSC create a possibility for deciphering molecular basis of this devastating neuromuscular disease.

Comparison of SMS-CTR eRMS (SMS) and CW9019 aRMS (CW) cell lines cultured under standard conditions. Expression of VEGF, VEGFR-1, VEGFR-2, HIF-1, HIF-2 and miR-146a genes.

Scheme showing the proposed relation between Pax3-FoxO1 induced expression of HO-1 and miR-206 dependent pathway.

Effect of miR-206 on expression of differentiation markers in SMS-CTR eRMS (SMS) and CW9019 aRMS (CW) cell lines.