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Population dynamics modeling reveals that myeloid bias involves both HSC differentiation and progenitor proliferation biases.
Blood
December 2024
UCLA Signaling Systems Laboratory, Los Angeles, California, United States.
Aging and chronic inflammation are associated with overabundant myeloid-primed multipotent progenitors (MPPs) amongst hematopoietic stem and progenitor cells (HSPCs). While HSC differentiation bias has been considered a primary cause of myeloid bias, whether it is sufficient has not been quantitatively evaluated. Here, we analyzed bone marrow data from the IκB- (Nfkbia+/-Nfkbib-/-Nfkbie-/-) mouse model of inflammation with elevated NFκB activity, which shows increased myeloid-biased MPPs.
View Article and Find Full Text PDFImmune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing.
Genes Immun
January 2025
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an exceptionally rare inflammatory disorder affecting choroid and retinal pigment epithelial (RPE) cells. Although recent studies suggest an immune-driven nature, the underlying etiology of APMPPE remains elusive. In this study, we conducted a comprehensive investigation on the peripheral blood mononuclear cells (PBMCs) profile of an APMPPE patient using single-cell RNA sequencing.
View Article and Find Full Text PDFApplication of Pathomic Features for Differentiating Dysplastic Cells in Patients with Myelodysplastic Syndrome.
Bioengineering (Basel)
December 2024
Department of Laboratory Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07440, Republic of Korea.
Myelodysplastic syndromes (MDSs) are a group of hematologic neoplasms accompanied by dysplasia of bone marrow (BM) hematopoietic cells with cytopenia. Recently, digitalized pathology and pathomics using computerized feature analysis have been actively researched for classifying and predicting prognosis in various tumors of hematopoietic tissues. This study analyzed the pathomic features of hematopoietic cells in BM aspiration smears of patients with MDS according to each hematopoietic cell lineage and dysplasia.
View Article and Find Full Text PDFTherapeutic potential of roxadustat in immune thrombocytopenia: A Mendelian randomization analysis.
J Thromb Haemost
January 2025
Hematology Department, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address:
Background: Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired megakaryocyte maturation. Hypoxia-inducible factor-1 alpha (HIF-1α), pivotal in the development of megakaryocytes and immune regulation, is downregulated in ITP. Roxadustat, which stabilizes HIF-1α, has emerged as a potential therapeutic drug for ITP that acts by enhancing HIF-1α-mediated megakaryocyte development and modulating immune responses.
View Article and Find Full Text PDFDeciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis.
Nat Commun
January 2025
Molecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
Ex vivo expansion of hematopoietic stem cells (HSC) requires the maintenance of a stemness state while cells are proliferating. This can be achieved via exposure to UM171 which leads to the degradation of chromatin modifiers and prevents the loss of key epigenetic marks. However, the chromatin landscape varies across populations within the hematopoietic system and the effect of UM171 on self-renewal and differentiation potential of different hematopoietic progenitor cells is less characterized.
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