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Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia.
J Exp Med
March 2025
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
Hematopoietic stem cells (HSCs) are susceptible to replication stress, which is a major contributor to HSC defects in Fanconi anemia (FA). Here, we report that HSCs relax the global chromatin by downregulating the expression of a chromatin architectural protein, DEK, in response to replication stress. DEK is abnormally accumulated in bone marrow (BM) CD34+ cells from patients with FA and in Fancd2-deficient HSCs.
View Article and Find Full Text PDFIn vitro ILC differentiation from human HSCs.
Methods Cell Biol
January 2025
Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
The Innate Lymphoid Cells (ILCs) are a family of innate immune cells composed by the Natural Killer (NK) cells and the helper ILCs (hILCs) (ILC1, ILC2, ILC3), both developing from a common ILC precursor (ILCP) derived from hematopoietic stem cells (HSCs). A correct ILC reconstitution is crucial, particularly in patients receiving HSC transplantation (HSCT), the only therapeutic option for many adult and pediatric high-risk hematological malignancies. Indeed, mainly thanks to their cytotoxic activity, NK cells have a strong Graft-versus-Leukemia (GvL) effect.
View Article and Find Full Text PDFAn Acellular Platform to Drive Urinary Bladder Tissue Regeneration.
Adv Ther (Weinh)
January 2025
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Center for Regenerative Nanomedicine, Northwestern University, Chicago, IL 60611, USA; Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA.
Impaired bladder compliance secondary to congenital or acquired bladder dysfunction can lead to irreversible kidney damage. This is managed with surgical augmentation utilizing intestinal tissue, which can cause stone formation, infections, and malignant transformation. Co-seeded bone marrow mesenchymal stem cell (MSC)/CD34+ hematopoietic stem cell (HSPC) scaffolds (PRS) have been successful in regenerating bladder tissue.
View Article and Find Full Text PDFRSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia.
Nat Commun
January 2025
Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation.
View Article and Find Full Text PDFLung long distance: histopathological changes in lung tissue after COVID-19 pneumonia.
Croat Med J
December 2024
Grgur Salai, University Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia,
Aim: To investigate histopathological changes in the lung tissue of long-COVID patients.
Methods: In this cross-sectional study, transbronchial lung biopsy was performed in long-COVID patients with persisting symptoms and radiological abnormalities. Histopathologic analyses were performed by using hematoxylin-eosin, Martius, Scarlet and Blue, Movat's, thyroid transcription factor 1, CD34, and CD68 staining.
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