美國科學(xué)家近日研究發(fā)現(xiàn),，與傳統(tǒng)的T細(xì)胞發(fā)育觀點(diǎn)不同，“青春期”細(xì)胞在轉(zhuǎn)變成成熟免疫細(xì)胞的過程中,，并不僅僅限于發(fā)育成T細(xì)胞,，它們有可能發(fā)育成其它類型血細(xì)胞。這一發(fā)現(xiàn)將有助于更好地理解T細(xì)胞性白血病等疾病的產(chǎn)生原因,。相關(guān)論文發(fā)表在4月10日的《自然》（Nature）雜志上,。
T細(xì)胞和其它所有類型的血細(xì)胞均來源于骨髓中的造血干細(xì)胞（HSCs）。造血干細(xì)胞具有分化成血液中各種各樣細(xì)胞的能力,，分化的第一步則是轉(zhuǎn)變成多能祖細(xì)胞（MPPs）,。
關(guān)于接下來的分化過程，廣為接受的理論是存在兩條分化路徑,。一條稱為骨髓路徑,，即MPPs轉(zhuǎn)變成紅細(xì)胞和非淋巴白細(xì)胞的“先驅(qū)”；另一條稱為淋巴路徑,，即MPPs轉(zhuǎn)變成T細(xì)胞和B細(xì)胞的“先驅(qū)”,。而T細(xì)胞的先驅(qū)接著會(huì)進(jìn)入胸腺，在這里它們被稱作早胸腺祖細(xì)胞（ETPs）,。
論文高級(jí)作者,、賓夕法尼亞大學(xué)病理學(xué)教授Avinash Bhandoola表示：“如果目前關(guān)于T細(xì)胞發(fā)育的模型是正確的，那么ETPs就應(yīng)該只能產(chǎn)生T細(xì)胞,，而不能產(chǎn)生骨髓細(xì)胞（myeloid cells）,。”
研究人員對(duì)此進(jìn)行了驗(yàn)證,。他們首先應(yīng)用表面標(biāo)簽將小鼠胸腺里的ETPs與其它細(xì)胞分開，然后將每個(gè)ETP細(xì)胞進(jìn)行單獨(dú)培養(yǎng),，以觀察它們的分化情況,。
結(jié)果令人吃驚。大多數(shù)盛有單個(gè)ETP細(xì)胞的培養(yǎng)皿都充滿了T細(xì)胞和骨髓細(xì)胞,。這意味著大部分ETPs在進(jìn)入胸腺后并不僅限于轉(zhuǎn)變成T細(xì)胞,，它們?nèi)匀槐Ａ糁赥細(xì)胞和骨髓細(xì)胞間二選一的能力。接下來研究人員證實(shí)了,，在正常的胸腺中,，ETPs確實(shí)會(huì)產(chǎn)生骨髓細(xì)胞。Bhandoola說：“很難將觀測(cè)結(jié)果與過去我們對(duì)T細(xì)胞發(fā)育的看法協(xié)調(diào)起來,。”
論文第一作者,、賓夕法尼亞大學(xué)博士后Jeremiah Bell說：“弄清T細(xì)胞的生活史及確定MPPs轉(zhuǎn)變成T細(xì)胞的步驟極為重要。現(xiàn)在我們想要弄清的是,，ETPs怎樣作出決定,，以轉(zhuǎn)變成骨髓細(xì)胞或T細(xì)胞。雖然我們的研究著重于基本科學(xué),，但它有助于弄清早期祖細(xì)胞怎樣導(dǎo)致T細(xì)胞性白血病,。另外，胸腺中由ETPs產(chǎn)生的骨髓細(xì)胞也將引起我們的進(jìn)一步關(guān)注,。”（科學(xué)網(wǎng) 梅進(jìn)/編譯）
生物谷推薦原始出處：
（Nature）,，452, 764-767，J. Jeremiah Bell,，Avinash Bhandoola
The earliest thymic progenitors for T cells possess myeloid lineage potential
J. Jeremiah Bell1 & Avinash Bhandoola1
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Correspondence to: Avinash Bhandoola1 Correspondence and requests for materials should be addressed to A.B. (Email: [email protected]).
There exists controversy over the nature of haematopoietic progenitors of T cells. Most T cells develop in the thymus, but the lineage potential of thymus-colonizing progenitors is unknown. One approach to resolving this question is to determine the lineage potentials of the earliest thymic progenitors (ETPs). Previous work has shown that ETPs possess T and natural killer lymphoid potentials, and rare subsets of ETPs also possess B lymphoid potential1, suggesting an origin from lymphoid-restricted progenitor cells. However, whether ETPs also possess myeloid potential is unknown. Here we show that nearly all ETPs in adult mice possess both T and myeloid potential in clonal assays. The existence of progenitors possessing T and myeloid potential within the thymus is incompatible with the current dominant model of haematopoiesis, in which T cells are proposed to arise from lymphoid-2. Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered.
