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日本科學家的一項研究初步表明,T淋巴細胞和B淋巴細胞不是由同一類祖細胞分化而成。這一發現如果能被進一步證實,那么30年前提出的血液系統細胞分化路徑圖就可能需要修改了。
日本理化研究所日前發布新聞公報說,淋巴細胞一般分為T淋巴細胞和B淋巴細胞兩大類,有專家一直認為這兩者之間應該存在特別近的親緣關系。基于這一認識的血液系統細胞分化路徑圖所提出的造血過程是:造血干細胞分化出兩類祖細胞,一類祖細胞會分化為吞噬細胞和紅細胞等,另一類祖細胞會分化為T淋巴細胞和B淋巴細胞。
日本理化研究所的河本宏和京都大學教授桂義元10年前開發出了一種“多譜系起源分析法”,可分析單個細胞產生T淋巴細胞、B淋巴細胞和吞噬細胞的能力。兩人用這種方法分析了實驗鼠胎兒發育初期造血器官內的祖細胞,并根據分析結果提出了新的造血過程模型,即造血干細胞向T淋巴細胞、B淋巴細胞和紅細胞分化的過程中始終保持著產生吞噬細胞的能力。
這兩位研究人員說,現在他們利用基質細胞單層培養的新方法進行研究。這種方法比“多譜系起源分析法”能更有效地檢測到吞噬細胞的生成。研究人員使用新方法逐個測定實驗鼠胸腺內祖細胞的分化能力,結果表明,生成T淋巴細胞的祖細胞會喪失分化成B淋巴細胞的能力,卻依然保持著產生巨噬細胞(吞噬細胞的一種)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,他們的相關論文已發表在新一期英國《自然》雜志上。
新聞公報說,這項成果不僅有助于研究細胞分化,對比較免疫學以及血液和免疫細胞進化的研究都可能產生較大影響。
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. (: 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.
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