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| http://dx.doi.org/10.1002/ajh.26251 | DOI Listing |
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A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.
Int J Mol Sci
January 2025
Department of Medicine V, Heidelberg University, 69117 Heidelberg, Germany.
To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).
View Article and Find Full Text PDFTET2-loss enhances immediate and time-resolved IFNγ signaling responses across myeloid differentiation.
Exp Hematol
January 2025
Department of Medicine, Division of Hematology/Oncology & Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Nashville Veterans Affairs Hospital, Tennessee Valley Health Care, Department of Veterans Affairs, Nashville, TN. Electronic address:
Signaling responses to cytokines are disrupted in clonal hematopoiesis and myeloid malignancies. To better identify specific signaling response alterations in the presence or absence of TET2, we developed a 36-parameter CyTOF panel of both surface marker and phosphoprotein antigens in murine BM. We show diverse, cell-type specific inflammatory cytokine responses in healthy hematopoietic cells.
View Article and Find Full Text PDFGenetic evidence for the causal effect of clonal hematopoiesis on pulmonary arterial hypertension.
BMC Cardiovasc Disord
January 2025
Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, Hebei, China.
Background: Pulmonary arterial hypertension (PAH) is a severe and progressive cardiovascular disease. While potential links between clonal hematopoiesis (CH) and cardiovascular diseases have been identified, the causal relationship between CH and PAH remains unclear. This study aims to investigate the causal effect of CH on the risk of PAH using a two-sample Mendelian randomization (MR) approach.
View Article and Find Full Text PDFClonal hematopoiesis of indeterminate potential and type 2 diabetes mellitus among patients with STEMI: from a prospective cohort study combing bidirectional Mendelian randomization.
Cardiovasc Diabetol
January 2025
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, No.167, Beijing, 100037, China.
Aim: Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications and prognostic significance of CHIP and T2DM in patients diagnosed with ST-segment elevation myocardial infarction (STEMI).
Methods: Deep-targeted sequencing employing a unique molecular identifier (UMI) for the analysis of 42 CHIP mutations-achieving an impressive mean depth of coverage at 1000 × -was conducted on a cohort of 1430 patients diagnosed with acute myocardial infarction (473 patients with T2DM and 930 non-DM subjects).
Single-cell DNA sequencing reveals pervasive positive selection throughout preleukemic evolution.
Cell Genom
January 2025
Early Cancer Institute, University of Cambridge, Cambridge, UK. Electronic address:
The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees.
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