日本科學(xué)家的一項(xiàng)研究初步表明,,T淋巴細(xì)胞和B淋巴細(xì)胞不是由同一類(lèi)祖細(xì)胞分化而成。這一發(fā)現(xiàn)如果能被進(jìn)一步證實(shí),,那么30年前提出的血液系統(tǒng)細(xì)胞分化路徑圖就可能需要修改了,。
日本理化研究所日前發(fā)布新聞公報(bào)說(shuō),淋巴細(xì)胞一般分為T淋巴細(xì)胞和B淋巴細(xì)胞兩大類(lèi),,有專家一直認(rèn)為這兩者之間應(yīng)該存在特別近的親緣關(guān)系,。基于這一認(rèn)識(shí)的血液系統(tǒng)細(xì)胞分化路徑圖所提出的造血過(guò)程是:造血干細(xì)胞分化出兩類(lèi)祖細(xì)胞,,一類(lèi)祖細(xì)胞會(huì)分化為吞噬細(xì)胞和紅細(xì)胞等,,另一類(lèi)祖細(xì)胞會(huì)分化為T淋巴細(xì)胞和B淋巴細(xì)胞。
日本理化研究所的河本宏和京都大學(xué)教授桂義元10年前開(kāi)發(fā)出了一種“多譜系起源分析法”,,可分析單個(gè)細(xì)胞產(chǎn)生T淋巴細(xì)胞,、B淋巴細(xì)胞和吞噬細(xì)胞的能力。兩人用這種方法分析了實(shí)驗(yàn)鼠胎兒發(fā)育初期造血器官內(nèi)的祖細(xì)胞,,并根據(jù)分析結(jié)果提出了新的造血過(guò)程模型,,即造血干細(xì)胞向T淋巴細(xì)胞、B淋巴細(xì)胞和紅細(xì)胞分化的過(guò)程中始終保持著產(chǎn)生吞噬細(xì)胞的能力,。
這兩位研究人員說(shuō),,現(xiàn)在他們利用基質(zhì)細(xì)胞單層培養(yǎng)的新方法進(jìn)行研究。這種方法比“多譜系起源分析法”能更有效地檢測(cè)到吞噬細(xì)胞的生成,。研究人員使用新方法逐個(gè)測(cè)定實(shí)驗(yàn)鼠胸腺內(nèi)祖細(xì)胞的分化能力,,結(jié)果表明,,生成T淋巴細(xì)胞的祖細(xì)胞會(huì)喪失分化成B淋巴細(xì)胞的能力,卻依然保持著產(chǎn)生巨噬細(xì)胞(吞噬細(xì)胞的一種)的能力,。這表明河本宏和桂義元提出的模型很可能是正確的,,他們的相關(guān)論文已發(fā)表在新一期英國(guó)《自然》雜志上,。
新聞公報(bào)說(shuō),,這項(xiàng)成果不僅有助于研究細(xì)胞分化,對(duì)比較免疫學(xué)以及血液和免疫細(xì)胞進(jìn)化的研究都可能產(chǎn)生較大影響,。
生物谷推薦原始出處:
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: [email protected]).
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.