Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers. Further, we describe a FP-RMS mouse model driven by P3F expression and Cdkn2a loss in endothelial cells. Additionally, we show that P3F expression in TP53-null human iPSCs blocks endothelial-directed differentiation and guides cells to become myogenic cells that form FP-RMS tumors in immunocompromised mice. Together these findings demonstrate that FP-RMS can originate from aberrant development of non-myogenic cells driven by P3F.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651858 | PMC |
http://dx.doi.org/10.1038/s41467-023-43044-1 | DOI Listing |
ACS Biomater Sci Eng
December 2024
Department of Biomedical Engineering, University of North Texas, Denton, Texas 76207-7102, United States.
Liver tissues, composed of hepatocytes, cholangiocytes, stellate cells, Kupffer cells, and sinusoidal endothelial cells, are differentiated from endodermal and mesodermal germ layers. By mimicking the developmental process of the liver, various differentiation protocols have been published to generate human liver organoids (HLOs) in vitro using induced pluripotent stem cells (iPSCs). However, HLOs derived solely from the endodermal germ layer often encounter technical hurdles such as insufficient maturity and functionality, limiting their utility for disease modeling and hepatotoxicity assays.
View Article and Find Full Text PDFACS Biomater Sci Eng
December 2024
Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 16635-148, Iran.
To enhance therapeutic strategies for cardiovascular diseases, the development of more reliable in vitro preclinical systems is imperative. These models, crucial for disease modeling and drug testing, must accurately replicate the 3D architecture of native heart tissue. In this study, we engineered a scaffold with aligned poly(lactic--glycolic acid) (PLGA) microfilaments to induce cellular alignment in the engineered cardiac microtissue (ECMT).
View Article and Find Full Text PDFInt J Nanomedicine
December 2024
Key Laboratory of Bioresources and Eco-Environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, People's Republic of China.
Introduction: The proliferation of nanoplastics (NPs) has emerged as a significant environmental concern due to their extensive use, raising concerns about potential adverse effects on human health. However, the exact impacts of NPs on the early development of hematopoietic organs remain poorly understood.
Methods: This investigation utilized fluorescence microscopy to observe the effects of various NP concentrations on the caudal vein plexus (CVP) development in zebrafish embryos.
Front Bioeng Biotechnol
December 2024
Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Introduction: Extensive trauma frequently disrupts endometrial regeneration by diminishing endometrial stem cells/progenitor cells, affecting female fertility. While bone marrow mesenchymal stem cell (BMSC) transplantation has been suggested as an approach to address endometrial injury, it comes with certain limitations. Recent advancements in endometrial epithelial organoids (EEOs) have displayed encouraging potential for endometrial regeneration.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Department of Central Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong, China.
Background: The simultaneous differentiation of human pluripotent stem cells (hPSCs) into both endodermal and mesodermal lineages is crucial for developing complex, vascularized tissues, yet poses significant challenges. This study explores a method for co-differentiation of mesoderm and endoderm, and their subsequent differentiation into pancreatic progenitors (PP) with endothelial cells (EC).
Methods: Two hPSC lines were utilized.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!