Shwachman-Diamond Syndrome (SDS) is a rare and clinically-heterogeneous bone marrow (BM) failure syndrome caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Although SDS was described over 50 years ago, the molecular pathogenesis is poorly understood due, in part, to the rarity and heterogeneity of the affected hematopoietic progenitors. To address this, we used single cell RNA sequencing to profile scant hematopoietic stem and progenitor cells from SDS patients. We generated a single cell map of early lineage commitment and found that SDS hematopoiesis was left-shifted with selective loss of granulocyte-monocyte progenitors. Transcriptional targets of transforming growth factor-beta (TGFβ) were dysregulated in SDS hematopoietic stem cells and multipotent progenitors, but not in lineage-committed progenitors. TGFβ inhibitors (AVID200 and SD208) increased hematopoietic colony formation of SDS patient BM. Finally, TGFβ3 and other TGFβ pathway members were elevated in SDS patient blood plasma. These data establish the TGFβ pathway as a novel candidate biomarker and therapeutic target in SDS and translate insights from single cell biology into a potential therapy.
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http://dx.doi.org/10.1172/JCI125375 | DOI Listing |
Sci Rep
December 2024
Department of Electrical Engineering, College of Engineering, King Saud University, Riyadh, 11421, Saudi Arabia.
The world is moving towards the utilization of hydrogen vehicle technology because its advantages are uniformity in power production, more efficiency, and high durability when compared to fossil fuels. So, in this work, the Proton Exchange Membrane Fuel Stack (PEMFS) device is selected for producing the energy for the hydrogen vehicle. The merits of this fuel technology are the possibility of operating less source temperature, and more suitability for stationery and transportation applications.
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December 2024
Laboratory of Biochemistry and Vascular Biology, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, 20993, MD, USA.
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December 2024
Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Lines of evidence have indicated that type 2 diabetes mellitus (T2DM) is an independent risk factor for osteoarthritis (OA) progression. However, the study focused on the relationship between T2DM and OA at the transcriptional level remains empty. We downloaded OA- and T2DM-related bulk RNA-sequencing and single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) dataset.
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December 2024
Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kocaeli University Hospital, Kocaeli, Turkey.
Background: Hematological markers such as the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are reliable indicators of inflammation. This study aims to investigate the potential role of these markers in assessing disease activity and treatment response in biologic-naive Ankylosing Spondylitis (AS) patients following the initiation of biological agents.
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Sci Rep
December 2024
Department of Neurology, Union Hospital of Jilin University, Changchun, 130000, China.
Alzheimer's disease (AD) is a severe neurodegenerative disease, and the most common type of dementia, with symptoms of progressive cognitive dysfunction and behavioral impairment. Studying the pathogenesis of AD and exploring new targets for the prevention and treatment of AD is a very worthwhile challenge. Accumulating evidence has highlighted the effects of fatty acid metabolism on AD.
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