Koide Shuhei, Sigurdsson Valgardur, Radulovic Visnja, Saito Kiyoka, Zheng Zhiqian, Lang Stefan, Soneji Shamit, Iwama Atsushi, Miharada Kenichi
Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 108-0071 Tokyo, Japan.
iScience. 2021 Dec 10;25(1):103603. doi: 10.1016/j.isci.2021.103603. eCollection 2022 Jan 21.
Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after culture. Here we show that cultured HSCs express mast cell-related genes including . After culture, phenotypic HSCs were divided into CD244 and CD244 subpopulations, and only CD244 cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the CD244 subpopulation, whereas ER stress suppression using a molecular chaperone, TUDCA, decreased CD244 population, which was correlated to improved reconstitution output. These data suggest CD244 is a potent marker to exclude non-functional HSCs after culture thereby useful to elucidate mechanism of functional decline of HSCs during treatment.
利用具有多种细胞表面标志物的流式细胞术可以分离长期造血干细胞（HSC）。然而，这些细胞表面表型在培养后并不代表功能性造血干细胞。在这里，我们表明培养的造血干细胞表达包括……在内的肥大细胞相关基因。培养后，表型造血干细胞被分为CD244和CD244亚群，只有肥大细胞基因表达低且维持造血干细胞相关基因的CD244细胞具有重建潜力。当造血干细胞在含有聚乙烯醇的高效扩增培养基中培养时，结果相同。化学诱导的内质网（ER）应激信号增加了CD244亚群，而使用分子伴侣TUDCA抑制内质网应激则减少了CD244群体，这与改善的重建输出相关。这些数据表明，CD244是排除培养后无功能造血干细胞的有效标志物，因此有助于阐明造血干细胞在治疗过程中功能下降的机制。
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