AI Article Synopsis
Article Abstract
Therapeutic application of human embryonic stem cells (hESCs) requires precise control over their differentiation. However, spontaneous differentiation is prevalent, and growth factors induce multiple cell types; e.g., the mesoderm inducer BMP4 generates both mesoderm and trophoblast. Here we identify endogenous WNT signals as BMP targets that are required and sufficient for mesoderm induction, while trophoblast induction is WNT independent, enabling the exclusive differentiation toward either lineage. Furthermore, endogenous WNT signals induce loss of pluripotency in hESCs and their murine counterparts, epiblast stem cells (EpiSCs). WNT inhibition obviates the need to manually remove differentiated cells to maintain cultures and improves the efficiency of directed differentiation. In EpiSCs, WNT inhibition stabilizes a pregastrula epiblast state with novel characteristics, including the ability to contribute to blastocyst chimeras. Our findings show that endogenous WNT signals function as hidden mediators of growth factor-induced differentiation and play critical roles in the self-renewal of hESCs and EpiSCs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297870 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2014.11.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Wnt7a is required for regeneration of dystrophic skeletal muscle.
Skelet Muscle
December 2024
Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.
Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression in mdx muscle, a model for Duchenne muscular dystrophy (DMD). Here, we assessed muscle regeneration and function in wild type (WT) and mdx mice where Wnt7a was deleted in muscle using a conditional Wnt7a floxed allele and a Myf5-Cre driver. We found that both WT and mdx mice lacking Wnt7a in muscle, exhibited marked deficiencies in muscle regeneration at 21 d following cardiotoxin (CTX) induced injury.
View Article and Find Full Text PDFn-acetyl-l-cysteine stimulates bone healing by recovering the age-associated degenerative complications relative to osteoblastic Wntless ablation.
Biomed Pharmacother
December 2024
Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, South Korea; Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Jeonbuk National University, Jeonju 54896, South Korea. Electronic address:
Dysregulated Wnt signaling causes age-related characteristics such as oxidative stress, stem cell senescence, and abnormal bone homeostasis. Here we explored whether supplemental n-acetyl-l-cysteine (NAC) recovers the age-associated complications relative to osteoblastic Wntless (Wls) ablation and examined the possible mechanisms therein. For this work, we administered Col2.
View Article and Find Full Text PDFCircRNA-mediated heterogeneous ceRNA regulation mechanism in periodontitis and peri-implantitis.
Eur J Med Res
December 2024
Guangxi Medical University, Nanning, 530021, China.
Background: Performing a comprehensive study on the differential expression of mRNAs, miRNAs, and circRNAs in the context of peri-implantitis and periodontitis has beneficial advantages to identify unique molecular signatures and pathways that may contribute to our understanding of these conditions.
Methods: Gingival tissues from healthy individuals and peri-implantitis and periodontitis patients were obtained to identify differential expression genes (DEG) by Illumina HiSeq 2500 instrument. Differential expression analysis was conducted using R statistical software, with significance set at P < 0.
Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.
Oncogene
December 2024
Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
ZNRF3, a negative regulator of β-catenin signaling, removes Wnt receptors from the membrane. Currently, it is unknown which tumor-associated variants can be considered driver mutations and through which mechanisms they contribute to cancer. Here we show that all truncating mutations analyzed at endogenous levels exhibit loss-of-function, with longer variants retaining partial activity.
View Article and Find Full Text PDFEndogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling.
Elife
December 2024
Experimental Medicine II, Nikolaus-Fiebiger-Center, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay.
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!