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Biomedical subjects

Mariya Moosajee

Publications and source records attributed to Mariya Moosajee.

6 recordsLinked to original sources
PubMed2026

From stem cells to somites: Revealing genetic and exogenous factors of human embryogenesis.

Stem-cell-based human embryo models offer an ethically tractable platform for studying early human development. This study employs somitoids, three-dimensional models of human somitogenesis, to investigate how transcriptional programs and culture conditions influence somite formation and segmentation. We show that pre-differentiation culture medium impacts the developmental potential of induced pluripotent stem cells (iPSCs), with StemFit medium and Matrigel embedding outperforming mTeSR Plus medium in generating robust somite-like structures. Strikingly, these differences arise despite only subtle changes in transcriptomic and time-resolved proteomic profiles. P300-based proximity labeling also reveals a largely overlapping set of chromatin-associated regulators across iPSC conditions. In somitoids, enhancer-associated profiling highlights factors linked to somitogenesis, including MESP2 and TBX6. Knockout of three identified regulators, BPTF, RBPJ, and CITED2, demonstrate their essential roles in somite formation. Together, these findings highlight how culture conditions and enhancer-associated networks influence early human development and demonstrate somitoids as a scalable system for functional genomics.

Humans↗
PubMed2025

Sex Distributions in the Most Frequent Autosomal Genetic Causes of Retinitis Pigmentosa.

PURPOSE: The purpose of this study was to explore whether sex imbalances are detectable in the most frequent genetic causes of retinitis pigmentosa (RP). METHODS: Databases from centers in three countries (Moorfields Eye Hospital, London; Hospital for Sick Children, Toronto; and Australian Inherited Retinal Disease Registry, Perth, Australia) were searched, quantifying numbers of male and female patients with disease attributed to variants in the six most frequently involved autosomal RP genes. Proportions of female patients (with 95% confidence intervals [CIs]) were calculated for each gene. Two-tailed binomial testing was performed (Bonferroni corrected threshold, P = 0.008) to investigate whether proportions differed significantly from an underlying male:female ratio of 1:1. For genes where the 95% CI did not include 50%, sex distributions were also explored in previously published cohorts. RESULTS: Our search yielded 1454 patients with disease attributable to variants in USH2A (n = 550), RP1 (n = 277), RHO (n = 246), PRPF31 (n = 158), EYS (n = 124), and MYO7A (n = 99). Proportions of female patients (95% CI) for each gene were 46.2% (42.0-50.5%), 49.5% (43.4-55.5%), 55.3% (48.8-61.6%), 63.9% (55.9-71.3%), 39.5% (31.0-48.7%), and 42.4% (32.7-52.8%), respectively. The 95% CI did not include 50% for PRPF31 and EYS; binomial testing revealed P values of 6.24 × 10-4 and 0.025, respectively. Combining with data extracted from previously published cohorts yielded P values of 1.62 × 10-6 and 0.0084, respectively. CONCLUSIONS: We observed a significant preponderance of female patients for PRPF31-associated RP and a preponderance of male patients in those with EYS-associated RP. Our findings suggest that sex is likely to be a modifier affecting penetrance in PRPF31-associated disease and might act in the opposite direction in disease associated with EYS.

Humans↗
PubMed2005

Genes and the eye.

Explore the source record for details and available documents.

Eye Diseases, Hereditary↗
PubMed2003

Transcriptional regulation and expression of the dominant drusen gene FBLN3 (EFEMP1) in mammalian retina.

PURPOSE: To determine the important transcriptional control elements and sites of expression of fibulin-3 in mammalian retina. METHODS: Sequencing and 5' rapid amplification of cDNA ends (RACE) were undertaken to characterize the genomic sequence upstream of the FBLN3 coding sequence. Reporter deletion-mutation constructs were used in luciferase transfection assays to determine the important regulatory motifs. Fibulin-3 expression in mouse and human retina was studied by in situ hybridization and RT-PCR. The effect of 17beta-estradiol on fibulin-3 production was studied in COS-7 and ARPE-19 cells. RESULTS: Two untranslated exons were fully sequenced completing the characterization of FBLN3 that comprises 12 exons. Reporter assays suggest that the FBLN3 proximal promoter is contained within 425 bp upstream of exon 1. Important regulatory elements include three Sp1-binding sites, a Tant motif (trans-activating) and an estrogen response element (ERE) binding site (trans-repressing). No TATA or CAAT regulatory boxes were identified. RT-PCR suggests that the fibulin-3 gene is expressed in murine and human RPE, and in situ studies confirm that Fbln3 is expressed in the outer and inner nuclear layers, but strikingly not in the ganglion cell layer. Fibulin-3 expression in ARPE-19 cells could be modified by varying the amount of estrogen in the cell culture medium. CONCLUSIONS: The 5' end of the FBLN3 gene has been characterized, and the important upstream motifs regulating its transcription have been identified. Fibulin-3 is expressed in adult retina and at early stages in human and mouse development. Estrogen may be an important regulator of fibulin-3 expression, and this highlights a novel mechanism by which circulating estrogen may control the composition of the retinal extracellular matrix.

Animals↗