Biology subjects

Magistretti, P.

Publications and source records attributed to Magistretti, P..

4 recordsLinked to original sources

bioRxiv2026

Establishment of the Saudi Bank of Induced Pluripotent Stem Cells (SBiPSCs): A National Platform for iPSC-Based Research and Therapy

BackgroundThe global landscape of induced pluripotent stem cell (iPSC) resources remains heavily skewed toward European, North American, and East Asian populations, leaving the Middle East and North Africa (MENA) region critically underrepresented. This disparity hinders the application of precision medicine in populations with unique genetic backgrounds, particularly those with high rates of consanguinity and distinctive rare disease profiles. To address this gap, we established the Saudi Bank of Induced Pluripotent Stem Cells (SBiPSCs), at King Abdullah International Medical Research Centre (KAIMRC). The bank comprises two major complementary arms: one dedicated to the derivation and biobanking of iPSCs from individuals with rare and common genetic disorders, and a second focused on Human Leukocyte Antigen (HLA)-based iPSC banking to support the development of immunocompatible cell therapies. MethodsSBiPSCs operates within King Abdulaziz Medical City in Jeddah under the Ministry of National Guard for Health Affairs (MNGHA)s ethical and clinical framework. To establish the repository, we implemented a clinic-guided enrolment strategy in which treating physicians, briefed on the banks objectives, recruited patients with confirmed genetic diagnoses. Peripheral blood samples were collected, processed, and cells were reprogrammed using non-integrating episomal plasmids. All derived lines underwent rigorous quality control in accordance with International Society for Stem Cell Research (ISSCR) standards, including assessment of pluripotency markers, genomic integrity, and trilineage differentiation potential. To demonstrate our iPS characterization workflow and translational utility, iPSCs from a Saudi patient with familial Long QT Syndrome (LQTS) and a healthy sibling were differentiated into functional cardiac organoids. Simultaneously, for the HLA-based banking arm, the Saudi Stem Cell Donor Registry (SSCDR) database was leveraged to identify donors predicted to provide maximal coverage for the Saudi population. ResultsTo date, SBiPSCs has successfully generated 37 iPSC lines derived from 19 Saudi patients and healthy donors. All lines exhibit robust expression of pluripotency markers, maintain normal karyotypes, and demonstrate differentiation capacity. To demonstrate our characterization pipeline and translational utility, iPSCs from an LQTS patient and a healthy sibling were generated, validated, and differentiated into beating cardiac organoids that recapitulated the disease phenotype, with microelectrode array analysis confirming prolonged field potential durations mirroring the clinical QT prolongation. Furthermore, the HLA-based banking arm has expanded to include two homozygous iPSC lines, which together provide immunological compatibility for approximately 9% of the Saudi population. ConclusionsSBiPSCs represents the first centralized iPSC repository in the MENA region. The SBiPSCs is well-positioned to accelerate the translation of stem cell research into scalable, immunocompatible cell therapies and precision medicine applications aligned with national and regional healthcare priorities.

genetics↗

bioRxiv2024

Platelet-derived LPA16:0 inhibits adult neurogenesis and stress resilience in anxiety disorder

Anxiety disorders are accompanied by changes in brain plasticity, stress vulnerability and heightened risk of depression. Here, we found that serum LPA16:0 abundance increased with trait anxiety in both human and mice and was sufficient to reduce the proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor, LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreased hippocampal neurogenesis and stress resilience, whereas LPA1 antagonism or the reduction of platelets, the main source of circulating LPA16:0, increased adult neurogenesis and resilience to acute stress. Finally, the inhibition of adult neurogenesis abolished the beneficial effect of LPA1 antagonism on resilience against both acute and chronic stress. Together, these findings identify LPA16:0-LPA1 signaling as a regulation mechanism of adult neurogenesis and a potential therapeutic target for mood disorders.

neuroscience↗

bioRxiv2022

Ultraliser: a framework for creating multiscale, high-fidelity and geometrically realistic 3D models for in silico neuroscience

UO_SCPLOWLTRALISERC_SCPLOW is a neuroscience-specific software framework capable of creating accurate and biologically realistic 3D models of complex neuroscientific structures at intracellular (e.g. mitochondria and endoplasmic reticula), cellular (e.g. neurons and glia) and even multicellular scales of resolution (e.g. cerebral vasculature and minicolumns). Resulting models are exported as triangulated surface meshes and annotated volumes for multiple applications in in silico neuroscience, allowing scalable supercomputer simulations that can unravel intricate cellular structure-function relationships. UO_SCPLOWLTRALISERC_SCPLOW implements a high performance and unconditionally robust voxelization engine adapted to create optimized watertight surface meshes and annotated voxel grids from arbitrary non-watertight triangular soups, digitized morphological skeletons or binary volumetric masks. The framework represents a major leap forward in simulation-based neuroscience, making it possible to employ high-resolution 3D structural models for quantification of surface areas and volumes, which are of the utmost importance for cellular and system simulations. The power of UO_SCPLOWLTRALISERC_SCPLOW is demonstrated with several use cases in which hundreds of models are created for potential application in diverse types of simulations. UO_SCPLOWLTRALISERC_SCPLOW is publicly released under the GNU GPL3 license on GitHub (BlueBrain/Ultraliser). SignificanceThere is crystal clear evidence on the impact of cell shape on its signaling mechanisms. Structural models can therefore be insightful to realize the function; the more realistic the structure can be, the further we get insights into the function. Creating realistic structural models from existing ones is challenging, particularly when needed for detailed subcellular simulations. We present UO_SCPLOWLTRALISERC_SCPLOW, a neuroscience-dedicated framework capable of building these structural models with realistic and detailed cellular geometries that can be used for simulations. Key pointsO_LIUltraliser creates spatial models of neuro-glia-vascular (NGV) structures with realistic geometries. C_LIO_LIUltraliser creates high fidelity watertight manifolds and large scale volumes from centerline descriptions, non-watertight surfaces, and binary masks. C_LIO_LIResulting models enable scalable in silico experiments that can probe intricate structure-function relationships. C_LIO_LIThe framework is unrivalled both in ease-of-use and in the accuracy of resulting geometry representing a major leap forward in simulation-based neuroscience. C_LI

bioinformatics↗

bioRxiv2022

Lactate supply overtakes glucose when neural computational and cognitive loads scale up

The neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads. Here, using electrophysiology, two-photon imaging, cognitive tasks and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting long-term synaptic plasticity evoked by high stimulation load activity patterns and high attentional load in cognitive tasks, and glucose being sufficient for less demanding neural computation and learning tasks. Overall, these results demonstrate that glucose and lactate metabolisms are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior. One sentence summaryNeuronal fueling by lactate versus glucose scales differently according to engram level and memory load.

neuroscience↗