Abstract Number: OC 08.2
Meeting: ISTH 2020 Congress
Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by isolated thrombocytopenia. A growing body of emerging evidence indicates that abnormalities during any stage of thrombopoiesis and megakaryocytopoiesis can influence platelet production.
Aims: Our study tried to find the abnormalities of hematopoietic stem and progenitor cells (HSPCs) in ITP patients from the perspective of single cell transcriptome.
Methods: CD34+ HSPCs were isolated from BM of four newly diagnosed ITP patients and 2 healthy adults as controls by fluorescence-activated cell sorter (FACS), and Single-cell RNA sequencing (scRNA-seq) data was collected using the recommended protocol for the 3′ scRNA-seq 10X genomics platform.
Results: We perform scRNA-seq for 50,375 single CD34+ HSPCs, and detected over 3000 expressed genes per cell on average. We visualized the cells in 2D space using t-distributed stochastic neighbor embedding (tSNE) (Fig1. a and Fig1. c). Heatmap showed the scaled expression of top 10 differentially expressed genes in each cluster (Fig1. b). Cell clusters expressed established markers of hematopoietic populations, revealed diverse hematopoietic cell types and implied differentiation trajectories consistent with current views of hematopoiesis. We identified an unambiguous feature of HSPCs in ITP patients with the up-regulation of the metallothionein family genes (MT2A, MT1G, MT1X, MT1E and MT1F)， which was most pronounced in megakaryocyte erythroid progenitor (Fig1. d). Metallothioneins (MTs), encoded by these genes, exhibit significant chelating properties and play a key role in trace elements homeostasis, protection against oxidative stress, and toxic heavy metals. Our study suggested that the metallothionein family genes were involved in the pathogenesis of ITP.
Conclusions: Using scRNA-seq, we revealed a hierarchically-structured transcriptional landscape of hematopoietic differentiation of BM CD34+ HSPCs. We observed a significantly increased expression of the metallothionein family genes in newly diagnosed ITP patients, which might relate with the generation of abnormal MKs and be a biomarker potentially using in diagnosis.
To cite this abstract in AMA style:Liu A, Wang S, Feng Q, Peng J. Features of Hematopoietic Stem and Progenitor Cells Identified through Single-Cell RNA Sequencing in Immune Thrombocytopenia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/features-of-hematopoietic-stem-and-progenitor-cells-identified-through-single-cell-rna-sequencing-in-immune-thrombocytopenia/. Accessed December 11, 2023.
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