Organogenesis and regeneration require coordination of cellular proliferation, regulated in part by secreted growth factors and cognate receptors, with tissue nutrient supply provided by expansion and patterning of blood vessels. Here we reveal unexpected combinatorial integration of a growth factor co-receptor with a heterodimeric partner and ligand known to regulate angiogenesis and vascular patterning. We show that ErbB2, which can mediate epidermal growth factor (EGF) and neuregulin signalling in multiple tissues, is unexpectedly expressed by endothelial cells where it partners with neuropilin 1 (Nrp1) to form a functional receptor for the vascular guidance molecule semaphorin 3d (Sema3d). Loss of Sema3d leads to improper patterning of the coronary veins, a phenotype recapitulated by endothelial loss of ErbB2. These findings have implications for possible cardiovascular side-effects of anti-ErbB2 therapies commonly used for cancer, and provide an example of integration at the molecular level of pathways involved in tissue growth and vascular patterning.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931334 | PMC |
http://dx.doi.org/10.1038/ncomms12038 | DOI Listing |
Elife
December 2024
Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Defining the cellular factors that drive growth rate and proteome composition is essential for understanding and manipulating cellular systems. In bacteria, ribosome concentration is known to be a constraining factor of cell growth rate, while gene concentration is usually assumed not to be limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, and modeling, we show that genome dilution in cells arrested for DNA replication limits total RNA polymerase activity within physiological cell sizes across tested nutrient conditions.
View Article and Find Full Text PDFCancer Chemother Pharmacol
December 2024
Departments of Pharmacology, Medicine Faculty, Sivas Cumhuriyet University, Sivas, Türkiye.
Purpose: Human epidermal growth factor-2 (HER-2) targeted drugs are used in only HER-2 overexpressed cancers. However, only a small portion of these cancer types are HER-2 overexpressed. In this study, we aimed to upregulate HER-2 receptors in MCF-7 breast cancer and HT-29 colon cancer cell cultures, which these cells are not HER-2 upregulated in natural status.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2024
Institute of Physiology, University Duisburg-Essen, Essen, Germany.
Over the last few decades, the primary cilium, an inconspicuous cell organelle, has increasingly become the focus of current research. The primary cilium is a microtubule-based, non-motile, antenna-like structure that is present on almost all mammalian cells. The ciliary membrane incorporates a large number of receptor molecules, which further characterize this cellular organelle.
View Article and Find Full Text PDFElife
December 2024
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.
A major challenge in the stem cell biology field is the ability to produce fully functional cells from induced pluripotent stem cells (iPSCs) that are a valuable resource for cell therapy, drug screening, and disease modelling. Here, we developed a novel inducible CRISPR-mediated activation strategy (iCRISPRa) to drive the expression of multiple endogenous transcription factors (TFs) important for in vitro cell fate and differentiation of iPSCs to haematopoietic progenitor cells. This work has identified a key role for IGFBP2 in developing haematopoietic progenitors.
View Article and Find Full Text PDFPhys Ther
December 2024
Leni and Peter W. May Department of Orthopaedics and Institute for Healthcare Delivery Science, Department of Population Health Science & Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Objective: Prehabilitation may have benefits for total hip arthroplasty (THA) and total knee arthroplasty (TKA), given an aging population with multimorbidity and the growth of value-based programs that focus on reducing postoperative costs. We aimed to describe prehabilitation use and examine predictors of utilization in fee-for-service Medicare beneficiaries.
Methods: This retrospective cohort study using the Medicare Limited Data Set included fee-for-service Medicare beneficiaries who were ≥ 66 years old and who underwent inpatient elective THA or TKA between January 1, 2016, and September 30, 2021.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!