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Although changes in mitochondrial morphology consistently associated with the aging of hematopoietic stem cells (HSCs), the specific molecular and cellular mechanisms involved are partially unclear. Live-cell super-resolution (SR) microscopy has been used to identify distinct HSC subsets that characterized by mitochondria unique morphologies and spatial distributions. The integration of SR microscopy with single-cell RNA sequencing enabled the classification of approximately 200 HSCs from young and aged mice into 5 discrete clusters. These clusters displayed molecular profiles that corresponded to the observed mitochondria states. An integrated approach combining RNA biomarker analysis and potential regulon assessment revealed previously unrecognized roles of GDF15 in mediating mitochondrial signals and morphologies that influence HSC fate. Thus, combining SR imaging with a bioinformatics pipeline provides an effective method for identifying key molecular players in specific phases of cellular transition, even with a relatively small dataset.
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http://dx.doi.org/10.1097/BS9.0000000000000236 | DOI Listing |
Front Immunol
September 2025
Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun, China.
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome that is caused primarily by immune-mediated destruction of hematopoietic stem cells. Traditional treatment relies on immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CSA). However, the toxicity and limited availability of ATG have spurred interest in ATG-free regimens.
View Article and Find Full Text PDFFront Immunol
September 2025
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
NSG-SGM3 humanized mouse models are well-suited for studying human immune physiology but are technically challenging and expensive. We previously characterized a simplified NSG-SGM3 mouse, engrafted with human donor CD34 hematopoietic stem cells without receiving prior bone marrow ablation or human secondary lymphoid tissue implantation, that still retains human mast cell- and basophil-dependent passive anaphylaxis responses. Its capacities for human antibody production and human B cell maturation, however, remain unknown.
View Article and Find Full Text PDFJ Exp Pharmacol
September 2025
Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
Purpose: Acute graft-versus-host disease (aGVHD) is a significant cause of death in recipients of allogeneic hematopoietic stem cell transplantation. In this type of graft, the intestine is particularly affected, with the loss of intestinal barrier integrity playing a key role in its onset. In this scenario, the aim of the present research was to evaluate defibrotide, a heparin-like compound, marked for severe veno-occlusive disease, as an innovative therapeutic approach for restoring intestinal barrier integrity using an in vitro model and analyzing aGVHD patients' sera and clinical data.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
September 2025
Department of Orthopedics I, Second Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.
Background: Emerging evidence indicates that lactase-mediated histone lactylation can activate osteogenic gene expression and promote bone formation. However, the role of lactylation-related genes (LRGs) in osteoporosis (OP) remains unclear. This study aims to clarify the key roles of LRGs and the molecular mechanisms of related biomarkers in OP.
View Article and Find Full Text PDFBlood Cell Ther
August 2025
Department of Haematology, Christian Medical College Vellore, Tamil Nadu, India.
Acute graft-versus-host disease (aGVHD) is a life-threatening complication that can develop after allogeneic hematopoietic stem cell transplantation. Patients with steroid-refractory aGVHD (SR-aGVHD) have an extremely poor prognosis. Ruxolitinib is an approved treatment for SR-aGVHD.
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