CRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based screens were conducted in cancer cell lines rather than healthy, differentiated cells. Here, we describe a CRISPR interference (CRISPRi)-based platform for genetic screens in human neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous genes in such neurons and present results from three complementary genetic screens. First, a survival-based screen revealed neuron-specific essential genes and genes that improved neuronal survival upon knockdown. Second, a screen with a single-cell transcriptomic readout uncovered several examples of genes whose knockdown had strikingly cell-type-specific consequences. Third, a longitudinal imaging screen detected distinct consequences of gene knockdown on neuronal morphology. Our results highlight the power of unbiased genetic screens in iPSC-derived differentiated cell types and provide a platform for systematic interrogation of normal and disease states of neurons. VIDEO ABSTRACT.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813890 | PMC |
| http://dx.doi.org/10.1016/j.neuron.2019.07.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Long-term epidemiological trends in (primary) pediatric central nervous system tumors: a 25-year cohort analysis in Western Mexico.
Childs Nerv Syst
January 2025
Ph.D. Human Genetics Program, Molecular Biology and Genomics Department, Human Genetics Institute "Dr. Enrique Corona-Rivera", University Center of Health Sciences, University of Guadalajara, Guadalajara, Mexico.
Background: Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited.
Methods: This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19 years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024.
Results: Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.
Are there atypical sites of IgG4 related disease in head and neck region? Personal experience and literature review.
Eur Arch Otorhinolaryngol
January 2025
Department of Otolaryngology and Head and Neck Surgery, IRCSS AOU San Martino, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy.
Purpose: Immunoglobulin G4-related disease (IgG4-RD) is a complex systemic fibroinflammatory condition with different clinical manifestations affecting multiple organ systems. Despite its rarity, the disease presents diagnostic and therapeutic challenges due to its mimicry of malignancies and other immune-mediated disorders. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease is the current state of art to confirm the diagnosis of IgG4-RD even in the absence of histological analysis.
View Article and Find Full Text PDFPrecision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: a systematic review.
Arch Orthop Trauma Surg
January 2025
Department of Orthopaedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.
Introduction: Liquid biopsy as a non-invasive method to investigate cancer biology and monitor residual disease has gained significance in clinical practice over the years. Whilst its applicability in carcinomas is well established, the low incidence and heterogeneity of bone and soft tissue sarcomas explains the less well-established knowledge considering liquid biopsy in these highly malignant mesenchymal neoplasms.
Materials And Methods: A systematic literature review adhering to the PRISMA guidelines initially identified 920 studies, of whom 68 original articles could be finally included, all dealing with clinical applicability of liquid biopsy in sarcoma.
Transcription factor MAZ activates the transcription of hypomethylated TYMP in ccRCC.
Funct Integr Genomics
January 2025
School of Medical Technology, Tianjin Medical University, Tianjin, 300203, China.
Clear cell renal cell carcinoma (ccRCC) is a highly malignant tumor characterized by a significant propensity for recurrence and metastasis. DNA methylation has emerged as a critical epigenetic mechanism with substantial utility in cancer diagnosis. In this study, multi-omics data were utilized to investigate the target genes regulated by the transcription factor MYC-associated zinc finger protein (MAZ) in ccRCC, leading to the identification of thymidine phosphorylase (TYMP) as a gene with notably elevated expression in ccRCC.
View Article and Find Full Text PDFIL-33, a neutrophil extracellular trap-related gene involved in the progression of diabetic kidney disease.
Inflamm Res
January 2025
Department of Nephrology, First Affiliated Hospital of Naval Medical University, Shanghai Changhai Hospital, Shanghai, China.
Background: Chronic inflammation is well recognized as a key factor related to renal function deterioration in patients with diabetic kidney disease (DKD). Neutrophil extracellular traps (NETs) play an important role in amplifying inflammation. With respect to NET-related genes, the aim of this study was to explore the mechanism of DKD progression and therefore identify potential intervention targets.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!