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Fadaili, Y.

Publications and source records attributed to Fadaili, Y..

2 recordsLinked to original sources

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↗

Canonical Wnt signalling from the Area Opaca induces and maintains the Marginal Zone in pre-primitive-streak stage chick embryos

In chick embryos prior to primitive streak formation, the outermost extraembryonic region, known as the area opaca (AO), was generally thought to act only by providing nutrients and mechanical support to the embryo. Just internal to the AO is a ring of epiblast called the marginal zone (MZ), separating the former from the inner, area pellucida epiblast. The MZ does not contribute cells to any part of the embryo but is involved in determining the position of primitive streak formation from the inner epiblast. Recently it was discovered that the AO can induce a MZ from area pellucida epiblast. Here we explore the nature of this inductive signal. We find that Wnt8c is highly expressed in the AO, whereas canonical Wnt pathway targets are enriched in the MZ, along with strong nuclear {beta}-catenin localization. Using isolation and recombination experiments combined with gain- and loss-of-function by exogenous chemical modulators of the pathway, we reveal that Wnt signalling is essential for induction and maintenance of the MZ, as well as sufficient to induce MZ properties in area pellucida epiblast. We propose that canonical Wnt signalling is responsible for induction of the marginal zone by the area opaca.

developmental biology↗