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The defective and persistent Sendai virus (SeVdp) vector system allows efficient generation of transgene-free induced pluripotent stem cells (iPSCs) from human somatic cells. By leveraging the system, here we report the generation of an iPSC line from somatic fibroblasts of a healthy control donner (female), named KEIOi002-A (also named YG-iPS). The control iPSC line would be a useful resource for stem cell research and regenerative medicine.

NGLY1 deficiency is a rare recessive genetic disease caused by mutations in the NGLY1 gene which codes for N-glycanase 1 (NGLY1). Here, we report the generation of two gene corrected iPSC lines using a patient-derived iPSC line (NCATS-CL6103) that carried a homozygous p.R401X mutation in the NGLY1 gene. These lines contain either one (NCATS-CL6104) or two (NCATS-CL6105) CRISPR/Cas9 corrected alleles of NGLY1. This pair of NGLY1 mutation corrected iPSC lines can be used as a control for the NCATS-CL6103 which serves as a cell-based NGLY1 disease model for the study of the disease pathophysiology and evaluation of therapeutics under development.

Human induced pluripotent stem cells (hiPSC) are considered promising sources of pancreatic islet organoids to treat diabetes. Due to that epigenetic memory predisposes iPSCs to enhanced differentiation into the parental cell type, we sought to generate iPSC lines from islet cells isolated from healthy adult pancreata. Islet cells were reprogrammed with CytoTune-iPS 2.0 Sendai Reprogramming Kit, where the generated iPSCs showed normal karyotype, expression of pluripotency associated markers and in vivo teratoma formation. This cell line will be a valuable resource for drug screening, and potential source for high-efficient generation of insulin-producing islets for treating diabetes.

Alport syndrome is the second most common genetic renal disease which caused by mutations in COL4A3/COL4A4/COL4A5, according to different modes of inheritance. Recently, we identified a novel homozygous mutation in COL4A3 gene in a patient with Alport syndrome. The Peripheral Blood Mononuclear Cells (PBMCs) of the patient were obtained and a line of induced pluripotent stem cells (iPSCs) was successfully generated. The iPSC line will be useful for further study of the pathogenesis and drug screening for Alport syndrome.

We have successively constructed several induced pluripotent stem cell (iPSC) lines of middle-aged and elderly male, but cell samples from young donors are still scarce. In this project, we recruited a healthy 29-year-old Chinese Han male, obtained his skin fibroblasts and successfully established iPSC line using non-integrated reprogramming technology. The iPSC line showed normal karyotype, expressed pluripotency markers and differentiated into three germ layers in vivo. The cell line will serve as an available control in the research of pathological mechanisms of early-onset neurological diseases.

Ataxia Telangiectasia is a rare autosomal recessive disorder caused by a mutated ATM gene. The most debilitating symptom of Ataxia Telangiectasia is the progressive neurodegeneration of the cerebellum, though the molecular mechanisms driving this degeneration remains unclear. Here we describe the generation and validation of an induced pluripotent stem cell (iPSC) line from an olfactory biopsy from a patient with Ataxia Telangiectasia. Sequencing identified two previously unreported disease-causing mutations in the ATM gene. This line can be used to generate 2D and 3D patient-specific neuronal models enabling investigations into the mechanisms underlying neurodegeneration.

Pathogenic bi-allelic variants in the SPG11 gene result in rare motor neuron disorders such as Hereditary Spastic Paraplegia type 11, Charcot-Marie Tooth, and Juvenile Amyotrophic Lateral Sclerosis-5. The main challenge in SPG11-linked disease research is the lack of antibodies against SPG11 encoded spatacsin. Here, we describe the CRISPR/Cas9 mediated generation and validation of an endogenously tagged SPG11- human iPSC line that contains an HA tag at the C-terminus of SPG11. The line exhibits multi-lineage differentiation potential and holds promise for studying the role of spatacsin and for the elucidation of SPG11-associated pathogenesis. Resource Table.

Alagille syndrome (ALGS) is a rare autosomal dominant disorder caused by disruption of the Notch signaling pathway due to mutations in either JAGGED1 (JAG1) (ALGS type 1) or NOTCH2 (ALGS type 2). Loss of this signaling interferes with the development of many organs, but especially the liver. A human induced pluripotent stem cell (iPSC) line was generated from the fibroblasts of a patient with a p. C312X (c. 936 T > A) variant in JAG1. This iPSC line offers a valuable resource to study the disease pathophysiology and develop therapeutics to treat patients with ALGS.

The generation of induced pluripotent stem cells (iPSCs) from healthy individuals is an invaluable resource as reference control in disease modeling and drug discovery. This paper details the reprogramming of peripheral blood mononuclear cells (PBMCs) isolated from a healthy 27 years-old male using non-integration technology. The derived iPSCs displayed typical pluripotent stem cell morphology, the capacity to differentiate into the three germ layers, and normal karyotype. This iPSC line will be used as a reference control to study the Cerebral Cavernous Malformation disease mechanism.

Hereditary hearing loss (HL) is the most common sensory disorder with multiple potential modes of inheritance, such as X-linked. Multiple loci have been associated with X-linked HL, including variants in the Small Muscle Protein X-Linked (SMPX) gene responsible for deafness, X-linked 4 (DFNX4) (OMIM 300066). Here we describe the derivation of an induced pluripotent stem cell (iPSC) line from an individual bearing a novel splice variant (c.133–1 G > A) that leads to a frameshift creating a premature stop codon (p.(Gly45Val*36)) in SMPX[1].

We have generated MLi004-A, a new induced pluripotent stem cell (iPSC) line derived from skin fibroblasts of a female patient with recessive dystrophic epidermolysis bullosa (RDEB). This iPSC line may be used as a model system for studies on skin integrity, the extracellular matrix and skin barrier function. The characterization of the MLi004-A cell line consisted of molecular karyotyping, next-generation sequencing of the COL7A1 alleles, plu-ripotency and differentiation potentials testing by immunofluorescence of associated markers in vitro. The MLi004-A line has been also tested for ability to differentiate into fibroblasts.

Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor‐intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high‐quality iPSC derivatives under controlled conditions. The current scale‐up methods used in cell therapy processes are based on empirical, geometry‐dependent methods that do not accurately represent the hydrodynamics of 3D bioreactors. These methods require multiple iterations of scale‐up studies, resulting in increased development cost and time. Here we show a novel approach using computational fluid dynamics modeling to effectively scale‐up cell therapy manufacturing processes in 3D bioreactors. Using a GMP‐compatible iPSC line, we translated and scaled‐up a small‐scale cardiomyocyte differentiation process to a 3‐L computer‐controlled bioreactor in an efficient manner, showing comparability in both systems., Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor‐intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high‐quality iPSC derivatives under controlled conditions.

Ocular albinism type 1 is a genetic eye disease caused by mutations in the GPR143 gene. Little is known about the molecular pathways involved in this disease and no therapeutic candidate has been identified as yet. Here we report the generation of an iPSC line from the skin fibroblasts of a patient with a mutation in the GPR143 gene using Sendai Virus vectors. This new iPSC line will allow a better understanding of the Ocular Albinism type 1 disease and to screen for potential therapeutic candidates.

International audience; We generated an induced pluripotent stem cell (iPSC) line using dermal fibroblasts from a patient with Usher syndrome type 2 (USH2). This individual was homozygous for the most prevalent variant reported in the USH2A gene, c.2299delG localized in exon 13. Reprogramming was performed using the non-integrative Sendai virus reprogramming method and the human OSKM transcription factor cocktail under feeder-free culture conditions. This iPSC line will be an invaluable tool for studying the pathophysiology of USH2 and for testing the efficacy of novel treatments.

Bardet-Biedl syndrome (BBS) is primarily a multisystem nonmotile ciliopathy. In this study, we describe the successful establishment and characterization of an iPSC line from a patient diagnosed with BBS who was compound heterozygous for the BBS7 variants c.849 + 1G > C (splicing) and c.754G > A (p.D252N).

Pathogenic mutations in the COL4A5 gene are the main causes of X-Linked Alport Syndrome (XLAS). Here, to better understand the pathogenic mechanism of XLAS, we generated an iPSC line (GWCMCi002-A) from the peripheral blood mononuclear cells (PBMCs) of an 8-year-old male XLAS patient with a hemizygous splicing mutation (NM_000495.4, c. 1517–1 G > T) in the COL4A5 gene. This cell line will be beneficial for the study of the pathogenic mechanism of XLAS and the development of treatment strategies.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessively inherited progressive retinal disease. Here, we describe the generation and characterization of a human induced pluripotent stem cell (hiPSC) line of BCD patient with CYP4V2 mutations. The reprogramming of this iPSC line was performed from skin fibroblast by using the Sendai-virus based approach. The established hiPSC line retained the disease-associated mutations and showed normal karyotype, pluripotency and differentiation capacity.

A human induced pluripotent stem cell (hiPSC) line (WMUi020-A) was generated from the aortic smooth muscle cells of a 56-year-old donor with bicuspid aortic valve and ascending aortic aneurysm. Episomal vector-mediated Non-integration iPSC reprogramming was used for this iPSC line generation. The established iPSC line highly expressed pluripotency markers with three germ-layer differentiation potential in vitro, as well as a normal karyotype. We further found that this iPSC line has a potential mutation of ROBO4 (c.161 T>C, p.Q54R), which may be useful for the disease modeling of bicuspid aortic valve aortopathy.

We report the genome-editing of an existing iPSC line carrying the London mutation in APP (V717I) into an iPSC line in which the pathogenic mutation was corrected. The resulting isogenic iPSC line maintained pluripotent stem cell morphology, a normal karyotype, expression of pluripotency markers and the ability to differentiate into the three germ-layers in vitro.

Variants in FBN1 are associated with Marfan Syndrome, an autosomal dominant disorder with clinical features that involve the musculoskeletal, cardiovascular and ocular systems. We generated a human iPSC line QDMHi001-A from a patient with Marfan syndrome and a heterozygous c.6772 T > C (p.Cys2258Arg) variant in FBN1. This line will be a valuable resource for in vitro disease modeling and drug testing for Marfan syndrome.

In this study we describe the generation and characterization of an human induced pluripotent stem cell (hiPSC) line from a long QT syndrome type 1 (LQT1) patient carrying the KCNQ1 c.940 G > A (p.Gly314Ser) mutation. This patient-specific iPSC line has been obtained by using non-integrational Sendai reprogramming method, expresses pluripotency markers and has the capacity to differentiate into the three germ layers and into spontaneously beating cardiomyocytes (iPSC-CMs).

Netherton syndrome (NS) is a rare, autosomal recessive hereditary skin disease caused by mutations in SPINK5 gene, characterized with severe skin barrier damage. A human induced pluripotent stem cell (iPSC) line has been established with electroporation method from urine-derived cells of a NS patient carrying a compound heterozygous mutation c.2260A > T (p.K754X) and c.2423C > T(p.T808I) in SPINK5 gene. This iPSC line may serve as a valuable model for the research of pathogenesis of NS, and the mechanisms and therapeutics for skin barrier damage.

Induced pluripotent stem cells (iPSCs) generated from young, healthy individuals are valuable tools for investigating molecular disease mechanisms during the early development of the brain vasculature. We generated an iPSC line from peripheral blood mononuclear cells (PBMCs) isolated from a healthy 13-yeard old female donor using the Sendai virus. The iPSCs differentiated into endothelial cells, astrocytes, and neurons. This iPSC line can serve as a healthy reference control for comparative studies in drug development and modeling the early onset of Cerebral Cavernous Malformation (CCM).

Ring chromosome 18 is a rare chromosomal disorders that usually originate de novo and correlate with clinical manifestation: developmental delay as well as microcephaly, brain and ocular malformations, hypotonia and skeletal abnormalities. We generate iPSC clonal cell line ICGi024-A with pluripotency properties which were demonstrated in vitro by three germ layer differentiation capacity. ICGi024-A can be used for disease modeling and fundamental investigation of ring chromosome instability.

Mutation in STING1 gene, which encodes stimulator of type I IFN gene (STING) leads to its constitutive activation and thereby to a severe vasculopathy and sometimes a lupus-like disease. We generated induced pluripotent stem cells (iPSCs) from a patient carrying a rare heterozygous variant c.463G > A (resulting in a p.V155M substitution) in STING1. Cells from this patient, which were reprogrammed by non-integrative viral transduction, had normal karyotype, expressed pluripotency markers and were able to differentiate into the three germ cell layers.

Summary Melanocytes, derived from neural crest cells, are involved in melanin production. This protocol describes a method to generate induced melanocytes (iMelanocytes) from human induced pluripotent stem cells (iPSCs) using a suspension culture system, which considerably improves the differentiation efficiency. The most critical parts of this protocol are the selection of a reliable iPSC line with strong potential to differentiate into melanocytes and their stemness maintenance. For complete information on the use and generation of this protocol, please refer to our Cell Reports article, Liu el al. (2019)., Graphical Abstract, Highlights • Selection of reliable iPSC lines and their stemness maintenance is critical • EB-based suspensive system enhances efficiency of iMelanocytes generation • EBs characterized by smooth borders and dark centers without cavities are preferred • Quality control is performed through morphology checks and melanocyte markers, Melanocytes, derived from neural crest cells, are involved in melanin production. This protocol describes a method to generate induced melanocytes (iMelanocytes) from human induced pluripotent stem cells (iPSCs) using a suspension culture system, which considerably improves the differentiation efficiency. The most critical parts of this protocol are the selection of a reliable iPSC line with strong potential to differentiate into melanocytes and their stemness maintenance.

miR-26b has been implicated in a wide range of human diseases, including cancer, diabetes, heart disease, Alzheimer’s disease and osteoarthritis. To provide a tool to explore the importance of miR-26b in this broad context, we have generated and characterized a homozygous miR-26b stem-loop knockout human iPSC line. This gene-edited line exhibited a normal karyotype, expressed pluripotency markers and differentiated into cells representative of the three embryonic germ layers. This iPSC line will be valuable for studies investigating disease mechanisms and testing therapeutic strategies in vitro.

Within the umbrella of mitochondrial disorders, Leigh’s disease is characterised as a rarer form with more than 80 genetic and mitochondrial DNA aberration variants. Here we report establishment of an induced pluripotent stem cell (iPSC) line from a 2.5 years old deceased female child, harbouring mutations in the NDUFV1 gene. One of the variants reported here is novel. The establishment of iPSC line allows development of a stable disease model for the specific variations, as there are no other cell/animal disease models for the same.