研究动态
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ABO 血型对红细胞生成有显著影响,导致 B 型血族群结局高红细胞压积的新证据出现了。

Novel evidence that the ABO blood group shapes erythropoiesis and results in higher hematocrit for blood group B carriers.

发表日期:2023 Feb 28
作者: Romy Kronstein-Wiedemann, Sarah Blecher, Madeleine Teichert, Laura Schmidt, Jessica Thiel, Markus M Müller, Jörn Lausen, Richard Schäfer, Torsten Tonn
来源: LEUKEMIA

摘要:

ABO血型系统对于输血和器官移植非常重要。由于相同转录因子和microRNA控制ABO血型抗原的表达并调节红细胞生成,我们假设这两个过程之间存在功能性联系。我们发现,与BG A相比,BG B血型献血者血红蛋白和红细胞比容值显著更高。此外,我们观察到,在BG B造血干/祖细胞(HSPCs)中,红细胞生成比BG A HSPCs更快。具体而言,BG B HSPCs在更短的时间内产生更多特定于细胞系的祖细胞(B:31.3±2.2% vs. A:22.5±3.0%)。此外,BG A之外的人群在末端分化的红细胞中含有更高的脱核率和更多的血红蛋白。此外,我们在红细胞BG B前体细胞中检测到miRNA-215-5p和-182-5p水平升高,以及它们的靶标转录因子RUNX1和HES-1 mRNA表达降低,表明这些因子在分化特异性糖基抗原消失和癌症特异性糖基抗原出现中的重要作用。我们的工作有助于更深入地了解红细胞生成基因调控网络,并确定其干扰BG特异性基因表达调控,特别是在疾病中,ABO BG确定治疗易感性和疾病进展。©2023年作者(们)。
The ABO blood group (BG) system is of great importance for blood transfusion and organ transplantation. Since the same transcription factors (TFs) and microRNAs (miRNAs) govern the expression of ABO BG antigens and regulate erythropoiesis, we hypothesized functional connections between both processes. We found significantly higher hemoglobin and hematocrit values in BG B blood donors compared to BG A. Furthermore, we observed that erythropoiesis in BG B hematopoietic stem/progenitor cells (HSPCs) was accelerated compared to BG A HSPCs. Specifically, BG B HSPCs yielded more lineage-specific progenitors in a shorter time (B: 31.3 ± 2.2% vs. A: 22.5 ± 3.0%). Moreover, non-BG A individuals exhibited more terminally differentiated RBCs with higher enucleation rates containing more hemoglobin compared to BG A. Additionally, we detected increased levels of miRNA-215-5p and -182-5p and decreased expression of their target TFs RUNX1 and HES-1 mRNAs in erythroid BG B precursor cells compared to BG A. This highlights the important roles of these factors for the disappearance of differentiation-specific glycan antigens and the appearance of cancer-specific glycan antigens. Our work contributes to a deeper understanding of erythropoiesis gene regulatory networks and identifies its interference with BG-specific gene expression regulations particularly in diseases, where ABO BGs determine treatment susceptibility and disease progression.© 2023. The Author(s).