日本科学家的一项研究初步表明,T淋巴细胞和B淋巴细胞不是由同一类祖细胞分化而成。这一发现如果能被进一步证实,那么30年前提出的血液系统细胞分化路径图就可能需要修改了。
日本理化研究所日前发布新闻公报说,淋巴细胞一般分为T淋巴细胞和B淋巴细胞两大类,有专家一直认为这两者之间应该存在特别近的亲缘关系。基于这一认识的血液系统细胞分化路径图所提出的造血过程是:造血干细胞分化出两类祖细胞,一类祖细胞会分化为吞噬细胞和红细胞等,另一类祖细胞会分化为T淋巴细胞和B淋巴细胞。
日本理化研究所的河本宏和京都大学教授桂义元10年前开发出了一种“多谱系起源分析法”,可分析单个细胞产生T淋巴细胞、B淋巴细胞和吞噬细胞的能力。两人用这种方法分析了实验鼠胎儿发育初期造血器官内的祖细胞,并根据分析结果提出了新的造血过程模型,即造血干细胞向T淋巴细胞、B淋巴细胞和红细胞分化的过程中始终保持着产生吞噬细胞的能力。
这两位研究人员说,现在他们利用基质细胞单层培养的新方法进行研究。这种方法比“多谱系起源分析法”能更有效地检测到吞噬细胞的生成。研究人员使用新方法逐个测定实验鼠胸腺内祖细胞的分化能力,结果表明,生成T淋巴细胞的祖细胞会丧失分化成B淋巴细胞的能力,却依然保持着产生巨噬细胞(吞噬细胞的一种)的能力。这表明河本宏和桂义元提出的模型很可能是正确的,他们的相关论文已发表在新一期英国《自然》杂志上。
新闻公报说,这项成果不仅有助于研究细胞分化,对比较免疫学以及血液和免疫细胞进化的研究都可能产生较大影响。
生物谷推荐原始出处:
Nature 452, 768-772 (10 April 2008) | doi:10.1038/nature06839;
Adult T-cell progenitors retain myeloid potential
Haruka Wada1,3, Kyoko Masuda1,3, Rumi Satoh1, Kiyokazu Kakugawa1, Tomokatsu Ikawa1, Yoshimoto Katsura1,2 & Hiroshi Kawamoto1
Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan
Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan
Present addresses: Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki 216-8512, Japan (H.W.); Institute of Molecular Medicine and Genetics, University of Georgia, GA 30602, USA (K.M.).
Correspondence to: Hiroshi Kawamoto1 Correspondence and requests for materials should be addressed to H.K. (Email: kawamoto@rcai.riken.jp).
During haematopoiesis, pluripotent haematopoietic stem cells are sequentially restricted to give rise to a variety of lineage-committed progenitors. The classical model of haematopoiesis postulates that, in the first step of differentiation, the stem cell generates common myelo-erythroid progenitors and common lymphoid progenitors (CLPs). However, our previous studies in fetal mice showed that myeloid potential persists even as the lineage branches segregate towards T and B cells1, 2, 3, 4, 5, 6. We therefore proposed the 'myeloid-based' model of haematopoiesis7, 8, in which the stem cell initially generates common myelo-erythroid progenitors and common myelo-lymphoid progenitors. T-cell and B-cell progenitors subsequently arise from common myelo-lymphoid progenitors through myeloid-T and myeloid-B stages, respectively. However, it has been unclear whether this myeloid-based model is also valid for adult haematopoiesis. Here we provide clonal evidence that the early cell populations in the adult thymus contain progenitors that have lost the potential to generate B cells but retain substantial macrophage potential as well as T-cell, natural killer (NK)-cell and dendritic-cell potential. We also show that such T-cell progenitors can give rise to macrophages in the thymic environment in vivo. Our findings argue against the classical dichotomy model in which T cells are derived from CLPs; instead, they support the validity of the myeloid-based model for both adult and fetal haematopoiesis.