The implications of stem cell heterogeneity for disease pathogenesis and therapy are poorly defined. JAK2V617F myeloproliferative neoplasms (MPNs), harboring the same mutation in hematopoietic stem cells (HSCs), display diverse phenotypes, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These chronic malignant disorders are ideal models to analyze the pathological consequences of stem cell heterogeneity. Single-cell gene expression profiling with parallel mutation detection demonstrated that the megakaryocyte (Mk)-primed HSC subpopulation expanded significantly with enhanced potential in untreated individuals with JAK2V617F ET, driven primarily by the JAK2 mutation and elevated interferon signaling. During treatment, mutant HSCs were targeted preferentially in the Mk-primed HSC subpopulation. Interestingly, homozygous mutant HSCs were forced to re-enter quiescence, whereas their heterozygous counterparts underwent apoptosis. This study provides important evidence for the association of stem cell heterogeneity with the pathogenesis and therapeutic response of a malignant disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.stem.2021.01.018 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluation of Reference Gene Stability for Investigations of Intracellular Signalling in Human Cancer and Non-Malignant Mesenchymal Stromal Cells.
Front Biosci (Schol Ed)
December 2024
Laboratory of Intracellular Membranes Dynamics, Institute of Cytology of the Russian Academy of Sciences, 194064 Saint Petersburg, Russia.
Background: Real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) is a powerful tool for analysing target gene expression in biological samples. To achieve reliable results by RT-qPCR, the most stable reference genes must be selected for proper data normalisation, particularly when comparing cells of different types. We aimed to choose the least variable candidate reference genes among eight housekeeping genes tested within a set of human cancer cell lines (HeLa, MCF-7, SK-UT-1B, A549, A431, SK-BR-3), as well as four lines of normal, non-malignant mesenchymal stromal cells (MSCs) of different origins.
View Article and Find Full Text PDFDevelopment of a Thermoresponsive Core-Shell Hydrogel for Sequential Delivery of Antibiotics and Growth Factors in Regenerative Endodontics.
Front Biosci (Elite Ed)
October 2024
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 1983969411 Tehran, Iran.
Background: Regenerative endodontics requires an innovative delivery system to release antibiotics/growth factors in a sequential trend. This study focuses on developing/characterizing a thermoresponsive core-shell hydrogel designed for targeted drug delivery in endodontics.
Methods: The core-shell chitosan-alginate microparticles were prepared by electrospraying to deliver bone morphogenic protein-2 for 14 days and transforming growth factor-beta 1 (TGF-β1) for 7-14 days.
Indoleamine-2,3-dioxygenase (IDO) Mediates the Suppression of T Cells by IFN-γ Primed Mesenchymal Stromal Cells in the Treatment of Psoriasis-Like Inflammation.
Front Biosci (Landmark Ed)
December 2024
Department of Pathology, The First Affiliated Hospital of Soochow University, 215123 Suzhou, Jiangsu, China.
Background: Psoriasis is a chronic and incurable skin inflammation driven by an abnormal immune response. Our study aims to investigate the potential of interferon-γ (IFN-γ) primed mesenchymal stem cells (IMSCs) in targeting T cells to attenuate psoriasis-like inflammation, and to elucidate the underlying molecular mechanism involved.
Methods: Mesenchymal stem cells (MSCs) were isolated from the umbilical cord and identified based on their surface markers.
Hybrid dark-field and attenuation contrast retrieval for laboratory-based X-ray tomography.
Optica
December 2024
Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK.
X-ray dark-field imaging highlights sample structures through contrast generated by sub-resolution features within the inspected volume. Quantifying dark-field signals generally involves multiple exposures for phase retrieval, separating contributions from scattering, refraction, and attenuation. Here, we introduce an approach for non-interferometric X-ray dark-field imaging that presents a single-parameter representation of the sample.
View Article and Find Full Text PDFA Magnetic-Responsive Biomimetic Nanosystem Coated with Glioma Stem Cell Membranes Effectively Targets and Eliminates Malignant Gliomas.
Biomater Res
December 2024
Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Glioblastoma multiforme (GBM) is among the most challenging malignant brain tumors, making the development of new treatment strategies highly necessary. Glioma stem cells (GSCs) markedly contribute to drug resistance, radiation resistance, and tumor recurrence in GBM. The therapeutic potential of nanomaterials targeting GSCs in GBM urgently needs to be explored.
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!