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Cone Rod Homeobox (): literature review and new insights.
Ophthalmic Genet
March 2025
Ophthalmic Genetics & Visual Function Branch, National Eye Institute, Bethesda, Virginia, USA.
The development of the neural retina requires a complex, spatiotemporally regulated network of gene expression. Here we review the role of the cone rod homeobox () transcription factor in specification and differentiation of retinal photoreceptors and its function in inherited retinal diseases such as cone-rod dystrophy (CoRD), dominant retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA). We delineate the findings of animal models and, more recently, human retinal organoids in elucidating molecular mechanisms of CRX activity and the pathogenesis of inherited photoreceptor degenerations.
View Article and Find Full Text PDFOxygen plays a critical role in early neural development in brains, particularly before establishment of complete vasculature; however, it has seldom been investigated due to technical limitations. This study uses an in vitro human cerebral organoid model with multiomic analysis, integrating advanced microscopies and single-cell RNA sequencing, to monitor tissue oxygen tension during neural development. Results reveal a key period between weeks 4 and 6 with elevated intra-organoid oxygen tension, altered energy homeostasis, and rapid neurogenesis within the organoids.
View Article and Find Full Text PDFProtocol for generating human cerebral organoids from two-dimensional cultures of pluripotent stem cells bypassing embryoid body aggregation.
STAR Protoc
March 2025
Unidad de Regeneración Neural, Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid 28220, Spain. Electronic address:
Human cerebral organoids (hCOs) provide an excellent model for the study of human brain development and disease. Here, we present a protocol to obtain hCOs directly from two-dimensional (2D) pluripotent stem cell (PSC) cultures, avoiding cell dissociation and posterior embryoid body (EB) aggregation. We describe steps for subjecting 2D cultures to a neural fate and subsequently developing hCOs.
View Article and Find Full Text PDFHair follicle neural crest stem cells reside in the bulge region of the outer root sheath of hair follicles, originate from the ectoderm, and have multidirectional differentiation potential, making them ideal candidates for tissue engineering applications. These cells mainly reside in a hypoxic microenvironment that favors the maintenance of stemness. Recently, many studies have elucidated the involvement of the Hippo pathway in the regulation of stem cell fate.
View Article and Find Full Text PDFSingle-cell transcriptomics has revolutionized our understanding of neurodevelopmental cell identities, yet, predicting a cell type's developmental state from its transcriptome remains a challenge. We perform a meta-analysis of developing human brain datasets comprising over 2.8 million cells, identifying both tissue-level and cell-autonomous predictors of developmental age.
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