Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Directed differentiation of human pluripotent stem cells (hPSCs) into somatic counterparts is a valuable tool for studying disease. However, examination of developmental mechanisms in hPSCs remains challenging given complex multi-factorial actions at different stages. Here, we used TALEN and CRISPR/Cas-mediated gene editing and hPSC-directed differentiation for a systematic analysis of the roles of eight pancreatic transcription factors (PDX1, RFX6, PTF1A, GLIS3, MNX1, NGN3, HES1, and ARX). Our analysis not only verified conserved gene requirements between mice and humans but also revealed a number of previously unsuspected developmental mechanisms with implications for type 2 diabetes. These include a role of RFX6 in regulating the number of pancreatic progenitors, a haploinsufficient requirement for PDX1 in pancreatic β cell differentiation, and a potentially divergent role of NGN3 in humans and mice. Our findings support use of systematic genome editing in hPSCs as a strategy for understanding mechanisms underlying congenital disorders.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892994 | PMC |
| http://dx.doi.org/10.1016/j.stem.2016.03.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ift140-Deficient Zebrafish as a Model for Kidney Cystogenesis and an F0-Based Screen for Genetic Modifiers of Kidney Cysts.
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
The FIBRILLIN multigene family in tomato, their roles in plastoglobuli structure and metabolism.
Plant J
September 2025
Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey, TW20 0EX, UK.
Plastoglobuli (PG) are plant lipoprotein compartments, present in plastid organelles. They are involved in the formation and/or storage of lipophilic metabolites. FIBRILLINs (FBNs) are one of the main PG-associated proteins and are particularly abundant in carotenoid-enriched chromoplasts found in ripe fruits and flowers.
View Article and Find Full Text PDFCRISPR RNP-Mediated Transgene-Free Genome Editing in Plants: Advances, Challenges and Future Directions for Tree Species.
Plant Cell Environ
September 2025
State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, Bamboo Research Institute, Key Laboratory of National Forestry and Grassland Administration on Subtropical Forest Biodiversity Conservation, School of Life Sciences, Nanjing Forestry
CRISPR ribonucleoprotein (RNP)-mediated genome editing offers a transgene-free platform for precise genetic modification in diverse herbaceous and tree species, including rice, wheat, apple, poplar, oil palm, rubber tree and grapevine. However, its application in woody plants faces distinct challenges, notably inefficient delivery and regeneration difficulties, particularly in species such as bamboo. While some of these issues also occur in herbaceous plants, they are often significantly more complex in woody species due to factors such as intricate cell wall architecture, widespread recalcitrant genotypes and inherent limitations of current delivery platforms.
View Article and Find Full Text PDFAbnormal zona pellucida and follicular development in -mutant macaques.
Zool Res
September 2025
College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. E-mail:
Zona pellucida glycoprotein-1 (ZP1) is essential for maintaining oocyte structural integrity and facilitating fertilization. Mutations in are strongly associated with primary infertility disorders such as fertilization failure and empty follicle syndrome; however, the absence of accurate experimental models has hindered mechanistic understanding and obscured the etiological basis of -related infertility. In this study, CRISPR/Cas9-mediated genome editing was employed to generate two -edited cynomolgus macaques ( ), designated #ZP1-1 (male) and #ZP1-2 (female).
View Article and Find Full Text PDFReduced Susceptibility to Phytophthora in Non-Transgenic Cacao Progeny Through CRISPR-Cas9 Mediated TcNPR3 Mutagenesis.
Plant Biotechnol J
September 2025
Huck Institutes of the Life Sciences, Penn State University, University Park, Pennsylvania, USA.
Black pod disease, caused by a complex of Phytophthora species, poses a severe threat to global cacao production. This study explores the use of CRISPR-Cas9 genome editing to reduce disease susceptibility in Theobroma cacao L. by targeting the TcNPR3 gene, a known negative regulator of plant defence.
View Article and Find Full Text PDF