Cellular function is shaped by transcriptional and post-transcriptional mechanisms, including alternative polyadenylation (APA). By directly controlling 3'- untranslated region (UTR) length and the selection of the last exon, APA regulates up to 70% of all cellular transcripts influencing RNA stability, output, and protein isoform expression. Cell-state-dependent 3'-UTR shortening has been identified as a hallmark of cellular proliferation. Hence, quiescent/dormant stem cells are characterized by long 3'-UTRs, whereas proliferative stem/progenitor cells exhibit 3'-UTR shortening. Here, the latest studies analyzing the role of APA in regulating stem cell state, self-renewal, differentiation, and metabolism are reviewed. The new role of APA in controlling stem cell fate opens novel potential therapeutic avenues in the field of regenerative medicine.
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http://dx.doi.org/10.1016/j.molmed.2021.04.006 | DOI Listing |
Blood Adv
January 2025
Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Interferon alpha (IFNa) is approved for the therapy of patients (pts) with polycythemia vera (PV), a subtype of myeloproliferative neoplasms (MPN). Some pts achieve molecular responses (MR), but clonal factors sensitizing for MR remain elusive. We integrated colony formation and differentiation assays with single-cell RNA seq and genotyping in PV-derived cells vs.
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January 2025
Univeristy of Alabama at Birmingham, Birmingham, Alabama, United States.
Hepatosplenic T-cell lymphoma (HSTCL) is an aggressive mature T-cell lymphoma characterized by significant hepatosplenomegaly, bone marrow involvement, and minimal or no lymphadenopathy. Primarily affecting young adults, it is exceptionally rare in children and adolescents. This makes diagnosis and treatment particularly challenging for pathologists and pediatric oncologists.
View Article and Find Full Text PDFPLoS One
January 2025
Center for Stem Cell and Regenerative Medicine, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan.
This study evaluated the effectiveness of a biosafety cabinet equipped with an ozone generator, particularly during the transition periods between the production of cell products. As living cell products cannot undergo sterilization, maintaining an aseptic manufacturing environment is paramount. Raw materials, often derived from human tissues, are frequently contaminated with various resident bacteria, necessitating environmental resets after each process.
View Article and Find Full Text PDFPLoS Biol
January 2025
Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial cells (HECs) within the developing embryo. Understanding the origin and ontogeny of HSPCs is of considerable interest and potential therapeutic value. It has been proposed that the murine placenta contains HECs that differentiate into HSPCs.
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January 2025
Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before.
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