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暨南大学兰雨课题组等发表造血干细胞发育研究成果

来源: Cell Research 作者:未知 点击数:326 时间:2017-05-10
  

      2017年4月28日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表了中国科学院军事医学科学院附属医院刘兵研究组和暨南大学基础医学院血液学研究所李扬秋团队兰雨研究员合作研究在造血干细胞发育的研究进展。研究题为“Clonal analysis reveals remarkable functional heterogeneity during hematopoietic stem cell emergence”的研究成果。兰雨和刘兵研究员为论文的共同通讯作者。

      近年来国际上多个研究组逐步揭示成体造血干细胞(hematopoietic stem cell, HSC)的功能异质性,然而人们对胚胎最早产生的造血干细胞是否具有功能异质性仍然缺乏认识。本研究首先发现胚胎最早发生的造血干细胞仅包括髓系相对缺陷型(γ型)及淋系髓系平衡型(β型)两种类型,后者较前者具有更高的重建嵌合能力和更强的自我更新潜能。而缺乏成体造血干细胞的另外两种类型,即淋系相对缺陷型(α型)和髓系绝对缺陷型(δ型)。此外,研究者发现造血干细胞前体(pre-HSC)的类型构成与同时期的成熟造血干细胞相同。最后,单细胞测序分析显示胚胎发育阶段相对于成体的造血干细胞大部分系列分化基因的表达水平更高。

      研究在国际上首次揭示小鼠胚胎发育中最早产生的造血干细胞以及造血干细胞前体即具有显著的功能异质性,从而完成整个生命周期造血干细胞功能异质性的图谱绘制(见下图),是他们继单细胞尺度解析造血干细胞起源(Nature, 2016)之后的又一重要科学发现。这些对于胚胎起源造血干细胞功能异质性的认识以及随之带来的对于造血干细胞异质性潜在内外调控机制的深度解析必将为造血干细胞再生研究提供重要的理论基础。

 

原文链接:

Clonal analysis reveals remarkable functional heterogeneity during hematopoietic stem cell emergence

原文摘要:

In conventional opinion, hematopoietic stem cells (HSCs) are alike, possessing robust self-renewal and multilineage differentiation capacity. However, growing evidence has revealed striking functional heterogeneity among individual HSCs, particularly in the aspect of lymphomyeloid output. Four subtypes of HSCs with distinct differentiation patterns have been identified and designated as α-, β-, γ-, and δ-HSCs. only lymphoid-deficient (α) and lymphomyeloid-balanced (β) HSCs bear durable engraftment potential and extensive self-renewal activity. Although differentiation program of individual HSCs can be stably self-propagated, occasional occurrence of inter-conversions among programs has also been observed. HSC heterogeneity exhibits developmental stage-related fluctuation, especially regarding the prevalence of α-HSCs, being minor in fetal liver but high in aging bone marrow (BM). The arising concept of HSC heterogeneity leads to a series of key questions, as to its embryonic origin, regulatory mechanisms, and relationship with leukemogenesis and therapeutics.

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