Even though gene repression is a powerful approach to exogenously regulate cellular behavior, developing a platform to effectively repress targeted genes, especially for stem-cell applications, remains elusive. Herein, we introduce a nanomaterial-based platform that is capable of mimicking the function of transcription repressor proteins to downregulate gene expression at the transcriptional level for enhancing stem-cell differentiation. We developed the "NanoScript" platform by integrating multiple gene repression molecules with a nanoparticle. First, we show a proof-of-concept demonstration using a GFP-specific NanoScript to knockdown GFP expression in neural stem cells (NSCs-GFP). Then, we show that a Sox9-specific NanoScript can repress Sox9 expression to initiate enhanced differentiation of NSCs into functional neurons. Overall, the tunable properties and gene-knockdown capabilities of NanoScript enables its utilization for gene-repression applications in stem cell biology.
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http://dx.doi.org/10.1002/anie.201504902 | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, 02912, USA.
Pulmonary hypertension (PH) increases the mortality of preterm infants with bronchopulmonary dysplasia (BPD). There are no curative therapies for this disease. Lung endothelial carnitine palmitoyltransferase 1a (Cpt1a), the rate-limiting enzyme of the carnitine shuttle system, is reduced in a rodent model of BPD.
View Article and Find Full Text PDFCell Rep
January 2025
Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. Electronic address:
Polycomb repressive complex 2 (PRC2), composed of the core subunits EED, SUZ12, and either EZH1 or EZH2, is critical for maintaining cellular identity in multicellular organisms. PRC2 deposits H3K27me3, which is thought to recruit the canonical form of PRC1 (cPRC1) to promote gene repression. Here, we show that EZH1-PRC2 and cPRC1 are the primary Polycomb complexes on target genes in non-dividing, quiescent cells.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemistry, Boston College, Chestnut Hill, MA, USA.
Recent advances in gene editing and precise regulation of gene expression based on CRISPR technologies have provided powerful tools for the understanding and manipulation of gene functions. Fusing RNA aptamers to the sgRNA of CRISPR can recruit cognate RNA-binding protein (RBP) effectors to target genomic sites, and the expression of sgRNA containing different RNA aptamers permit simultaneous multiplexed and multifunctional gene regulations. Here, we report an intracellular directed evolution platform for RNA aptamers against intracellularly expressed RBPs.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE; Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE; ASPIRE Precision Medicine Research Institute Abu Dhabi (PMRI-AD), United Arab Emirates University, Al Ain, UAE. Electronic address:
Neurodevelopmental disorders have complex origins that manifest early during embryonic growth and are associated with intricate gene regulation dynamics. A perturbed metabolic environment such as hyperglycemia or dyslipidemia, particularly due to maternal obesity, poses a threat to the optimal development of the embryonic central nervous system. Accumulating evidence suggests that these metabolic irregularities during pregnancy may alter neurogenesis pathways, thereby predisposing the developing fetus to neurodevelopmental disorders.
View Article and Find Full Text PDFDev Cell
January 2025
King's College London, Centre for Gene Therapy and Regenerative Medicine, School of Basic & Medical Biosciences, Faculty of Life Sciences and Medicine, London, UK; King's College London, Guy's Hospital Assisted Conception Unit, Department of Women and Children's Health, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, London, UK. Electronic address:
Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells.
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