Why Single-Cell Sequencing Has Promise in MDS.

Why Single-Cell Sequencing Has Promise in MDS.
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DOI:
10.3389/fonc.2021.769753
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发表时间:
2021
影响因子:
4.7
通讯作者:
Grimes HL
Grimes HL
中科院分区:
医学3区
文献类型:
--
作者:
Zhang X;Grimes HL

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骨髓增生异常综合征(MDS)是一组异质性疾病的特点是无效的造血。MDS的风险与衰老和造血干细胞和祖细胞(HSPC)中体细胞突变的积累有关。虽然过去十年DNA测序的进展揭示了MDS突变驱动的克隆选择,但尚不清楚HSPC在哪个阶段被捕获或什么阻止了成熟细胞的输出。近年来,单细胞测序技术通过识别经典造血层次阶段之间的过渡细胞状态,以及最重要的是细胞分化和谱系定型背后的生物学活动,彻底改变了我们对正常造血的理解。新兴的研究已经采用这些强大的工具来研究正常的造血以及骨髓恶性肿瘤的克隆异质性,并提供了一个渐进的疾病发病机制的描述。本文综述了增长的单细胞测序技术的潜力,不断发展的努力,以阐明造血在生理条件下和MDS在单细胞分辨率,并讨论他们如何可能填补我们目前的理解MDS生物学的差距。
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis. The risk of MDS is associated with aging and the accumulation of somatic mutations in hematopoietic stem cells and progenitors (HSPC). While advances in DNA sequencing in the past decade unveiled clonal selection driven by mutations in MDS, it is unclear at which stage the HSPCs are trapped or what prevents mature cells output. Single-cell-sequencing techniques in recent years have revolutionized our understanding of normal hematopoiesis by identifying the transitional cell states between classical hematopoietic hierarchy stages, and most importantly the biological activities behind cell differentiation and lineage commitment. Emerging studies have adapted these powerful tools to investigate normal hematopoiesis as well as the clonal heterogeneity in myeloid malignancies and provide a progressive description of disease pathogenesis. This review summarizes the potential of growing single-cell-sequencing techniques, the evolving efforts to elucidate hematopoiesis in physiological conditions and MDS at single-cell resolution, and discuss how they may fill the gaps in our current understanding of MDS biology.
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