Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Here, we show that conventional human pluripotent stem cells cultured with non-specific tankyrase-PARP1-inhibited conditions underwent proteogenomic reprogramming to functional blastomere-like tankyrase/PARP inhibitor-regulated naive stem cells (TIRN-SC). TIRN-SCs concurrently expressed hundreds of pioneer factors in hybrid 2C-8C-morula-ICM programs that were augmented by induced expression of DUX4. Injection of TIRN-SCs into 8C-staged murine embryos equipotently differentiated human cells to the extra-embryonic and embryonic compartments of chimeric blastocysts and fetuses. Ectopic expression of murine-E-Cadherin in TIRN-SCs further enhanced interspecific chimeric tissue targeting. TIRN-SC-derived trophoblast stem cells efficiently generated placental chimeras. Proteome-ubiquitinome analyses revealed increased TNKS and reduced PARP1 levels and an ADP-ribosylation-deficient, hyper-ubiquitinated proteome that impacted expression of both tankyrase and PARP1 substrates. ChIP-seq of NANOG-SOX2-OCT4 and PARP1 (NSOP) revealed genome-wide NSOP co-binding at DUX4-accessible enhancers of embryonic lineage factors; suggesting a DUX4-NSOP axis regulated TIRN-SC lineage plasticity. TIRN-SCs may serve as valuable models for studying the proteogenomic regulation of pre-lineage human embryogenesis. VIDEO ABSTRACT.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2025.115671 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recessive TMEM167A variants cause neonatal diabetes, microcephaly and epilepsy syndrome.
J Clin Invest
September 2025
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom.
Understanding the genetic causes of diseases affecting pancreatic β cells and neurons can give insights into pathways essential for both cell types. Microcephaly, epilepsy and diabetes syndrome (MEDS) is a congenital disorder with two known aetiological genes, IER3IP1 and YIPF5. Both genes encode proteins involved in endoplasmic reticulum (ER) to Golgi trafficking.
View Article and Find Full Text PDFMicroRNA-mediated regulation of proliferation, lineage differentiation, and apoptosis in neural stem cells.
RNA Biol
September 2025
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
Neural stem cells (NSCs) are multipotent stem cells with self-renewal capacity, able to differentiate into all neural lineages of the central nervous system, including neurons, oligodendrocytes, and astrocytes; thus, their proliferation and differentiation are essential for embryonic neurodevelopment and adult brain homoeostasis. Dysregulation in these processes is implicated in neurological disorders, highlighting the need to elucidate how NSCs proliferate and differentiate to clarify the mechanisms of neurogenesis and uncover potential therapeutic targets. MicroRNAs (miRNAs) are small, post-transcriptional regulators of gene expression involved in many aspects of nervous system development and function.
View Article and Find Full Text PDFHybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy.
Proc Natl Acad Sci U S A
September 2025
School of Medicine, Chongqing University, Chongqing 400044, China.
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion.
View Article and Find Full Text PDFModeling human retinal ganglion cell axonal outgrowth, development, and pathology using pluripotent stem cell-based microfluidic platforms.
Proc Natl Acad Sci U S A
September 2025
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202.
Retinal ganglion cells (RGCs) are highly compartmentalized neurons whose long axons serve as the sole connection between the eye and the brain. In both injury and disease, RGC degeneration occurs in a similarly compartmentalized manner, with distinct molecular and cellular responses in the axonal and somatodendritic regions. The goal of this study was to establish a microfluidic-based platform to investigate RGC compartmentalization in both health and disease states.
View Article and Find Full Text PDFThe Effects of Mesenchymal Stem Cell-Derived Exosomes on the Attenuation of Dry Eye Disease in Sjögren Syndrome Animal Model.
Tissue Eng Regen Med
September 2025
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, #505 BanPo-Dong, SeoCho-Gu, Seoul, 06591, Republic of Korea.
Background: Sjögren's syndrome (SS) is a chronic autoimmune disease delineated by excessive lymphocyte infiltration to the lacrimal or salivary glands, leading to dry eye and dry mouth. Exosomes secreted from mesenchymal stem cells (MSC) are known to have anti-inflammatory and tissue regeneration abilities. This study endeavored to demonstrate the effect of MSC-derived exosomes on the clinical parameter of dry eyes and associated pathology in SS mouse model.
View Article and Find Full Text PDF