A5066991759- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Neonatal Respiratory Health Research
- Molecular Biology Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Medical Imaging Techniques and Applications
- Tissue Engineering and Regenerative Medicine
- Evolution and Genetic Dynamics
- RNA regulation and disease
- Innovative Microfluidic and Catalytic Techniques Innovation
- Insect symbiosis and bacterial influences
- RNA and protein synthesis mechanisms
- Respiratory Support and Mechanisms
- Congenital Diaphragmatic Hernia Studies
- Nuclear Physics and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Renal and related cancers
- Protease and Inhibitor Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Congenital heart defects research
- Endoplasmic Reticulum Stress and Disease
- Genetic Syndromes and Imprinting
- Blood Coagulation and Thrombosis Mechanisms
- Animal Genetics and Reproduction
- Prion Diseases and Protein Misfolding
Institute for Regenerative Medicine & Biotherapy
2018-2024
Mary Lyon Centre at MRC Harwell
2016-2024
Université de Montpellier
2018-2022
Centre Hospitalier Universitaire de Montpellier
2022
Hôpital Saint Eloi
2020-2022
Inserm
2016-2021
Medical Research Council
2019
Institut Clinique de la Souris
2016
Université de Strasbourg
2016
Centre National de la Recherche Scientifique
2016
The success of the CRISPR/Cas9 genome editing technique depends on choice guide RNA sequence, which is facilitated by various websites. Despite importance and popularity these algorithms, it unclear to extent their predictions are in agreement with actual measurements.
Abstract The role of sex in biomedical studies has often been overlooked, despite evidence sexually dimorphic effects some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, found a large proportion mammalian traits both mutants are influenced by sex. This result implications interpreting disease phenotypes animal models humans.
Article15 May 2018Open Access Source DataTransparent process Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics amyotrophic lateral sclerosis Pietro Fratta Corresponding Author [email protected] orcid.org/0000-0002-8762-8188 UCL Institute Neurology, MRC Centre for Neuromuscular Disease, London, UK Search more papers by this author Prasanth Sivakumar Jack Humphrey Genetics Institute, Kitty Lo Thomas Ricketts Mammalian Unit, Harwell, Hugo Oliveira Jose...
Background: Nuclease-based technologies have been developed that enable targeting of specific DNA sequences directly in the zygote.These approaches provide an opportunity to modify genomes inbred mice, and allow removal strain-specific mutations confound phenotypic assessment.One such mutation is Cdh23 ahl allele, present several commonly used mouse strains, which predisposes age-related progressive hearing loss.Results: We targeted CRISPR/Cas9-mediated homology directed repair (HDR) correct...
Recent advances in clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing have led to the use of long single-stranded DNA (lssDNA) molecules for generating conditional mutations. However, there is still limited available data on efficiency and reliability this method. We generated mouse alleles using lssDNA donor templates performed extensive characterization resulting observed that as donors efficiently yielded founders bearing...
The obesity-linked FTO regulatory circuitry shows cross-species molecular, cellular, metabolic, and organismal conservation.
Abstract Background The application of CRISPR/Cas9 technology in human induced pluripotent stem cells (hiPSC) holds tremendous potential for basic research and cell-based gene therapy. However, the fulfillment these promises relies on capacity to efficiently deliver exogenous nucleic acids harness repair mechanisms by nuclease activity order knock-out or targeted genes. Moreover, transient delivery should be preferred avoid persistent decrease risk off-target events. We recently developed...
Karyotypic integrity is essential for the successful germline transmission of alleles mutated in embryonic stem (ES) cells. Classical methods identification aneuploidy involve cytological analyses that are both time consuming and require rare expertise to identify mouse chromosomes. As part International Mouse Phenotyping Consortium, we gathered data from over 1,500 ES cell clones found (GLT) efficiency compromised when 50 % cells harbour chromosome number abnormalities. In JM8 cells,...
Background Recent developments in CRISPR/Cas9 genome-editing tools have facilitated the introduction of precise alleles, including genetic intervals spanning several kilobases, directly into embryo. However, donor templates, via homology directed repair, can be erroneous or incomplete and these techniques often produce mosaic founder animals. Thus, newly generated alleles must verified at sequence level across targeted locus. Screening for presence desired mutant allele using traditional...
Background: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is complex disease with heterogeneous ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are promising tool to model human disease, including the impact genetic susceptibility. Methods: We developed simple reliable method for reprogramming peripheral blood mononuclear into hiPSCs differentiate them air–liquid interface bronchial epithelium within 45 days....
Half of the Chronic Obstructive Pulmonary Disease (COPD) patients started in early adulthood from a low lung function. In utero maternal smoking is associated with increased adult COPD risk. iPSCs offer an opportunity to model human development system. This project aimed model trajectories related developmental origin through two extreme groups i) onset COPD, and ii) free despite heavy smoking. Paired cultures airway epithelium were established at air-liquid interface (ALI) hiPSC...
The small EDRK-rich factor 2 (SERF2) is a highly conserved protein that modifies amyloid fibre assembly in vitro and promotes misfolding. However, the role of SERF2 regulating age-related proteotoxicity remains largely unexplored due to lack vivo models. Here, we report generation Serf2 knockout mice using an ES cell targeting approach, with alleles being bred onto different defined genetic backgrounds. We highlight phenotyping data from heterozygous Serf2+/- mice, including unexpected...
Abstract Recent developments in CRISPR/Cas9 genome editing tools have facilitated the introduction of more complex alleles, often spanning genetic intervals several kilobases, directly into embryo. These techniques produce mosaic founder animals and donor templates, via homologous directed repair, can be erroneous or incomplete. Newly generated alleles must verified at sequence level across targeted locus. Screening for presence desired mutant allele using traditional sequencing methods...
Abstract Adamts16 encodes a d isintegrin-like nd m etalloproteinase with t hrombo s pondin motifs, 16, member of family multi-domain, zinc-binding proteinases. ADAMTS-16 is implicated in number pathological conditions, including hypertension, cancer and osteoarthritis. A large observations, recent report human ADAMTS16 variants cases 46,XY disorders/differences sex development (DSD), also implicate this gene testis determination. We used CRISPR/Cas9 genome editing to generate...
Primary Ciliary Dyskinesia (PCD) is a rare heterogeneous genetic disorder affecting motile cilia structure and function leading to lung disease. We generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts of female PCD patient carrying disease-causing variants in the CCDC40 gene. Reprogramming was performed with human OSKM transcription factors using Sendai-virus delivery system. The resulting transgene free iPSCs had normal karyotype, expressed pluripotency markers, could...
Evidence highlights the concept of multiple trajectories leading to COPD. Early-life events (i.e., in utero lung development) may influence maximally attained function and increase risk develop Human pluripotent stem cells (hiPSC) represent a unique opportunity model development. We generated hiPSC lines from four highly characterized COPD patients with early onset severe phenotype. Peripheral blood mononuclear (PBMCs) were reprogrammed using integration-free Sendai Virus. The cell had...
Human pluripotent stem cells (hiPSC) are highly valuable tools to model lung development and chronic bronchial diseases. We generated a hiPSC line from characterized 40-year-old healthy male nonsmoking donor. Peripheral blood mononuclear (PBMCs) were reprogrammed using integration-free Sendai Virus. The cell had normal karyotype, expressed pluripotency hallmarks, differentiated into the three primary germ layers. reported UHOMi002-A iPSC may be used as control development, study human...
Human pluripotent stem cells (hiPSC) represent a unique opportunity to model lung development and chronic bronchial diseases. We generated hiPSC line from highly characterized healthy heavy smoker male donor free emphysema or tobacco related disease. Peripheral blood mononuclear (PBMCs) were reprogrammed using integration-free Sendai virus. The cell had normal karyotype, expressed pluripotency hallmarks, differentiated into the three primary germ layers. reported UHOMi007-A iPSC may be used...