造血干細(xì)胞產(chǎn)生兩種主要的祖細(xì)胞系：髓樣祖細(xì)胞(myeloid progenitor)和淋巴樣祖細(xì)胞(lymphoid progenitor),。圖片來自：Regenerative Medicine. Department of Health and Human Services. Chapter 2: Bone Marrow (Hematopoietic) Stem Cells. August 2006.
來自澳大利亞沃爾特與伊麗莎-霍爾研究所(Walter and Eliza Hall Institute)的研究人員在研究血液系統(tǒng)中應(yīng)對危機的細(xì)胞時得出一些令人吃驚的結(jié)論,，從而重新描繪體內(nèi)血細(xì)胞如何制造的“圖譜”,。這一發(fā)現(xiàn)可能對人們理解諸如骨髓增生性疾病(myeloproliferative disorder，它導(dǎo)致血細(xì)胞過量產(chǎn)生)之類的血液疾病和開發(fā)控制血細(xì)胞和凝血細(xì)胞如何產(chǎn)生的新方法有著廣泛的影響,。
該研究所癌癥和血液學(xué)部門Ashley Ng博士和Maria Kauppi博士領(lǐng)導(dǎo)的研究小組研究了一部分血祖細(xì)胞和導(dǎo)致它們增殖和產(chǎn)生成熟血細(xì)胞的信號,。2012年1月30日，他們的研究結(jié)果發(fā)表在PNAS期刊上,。
Ng博士將血祖細(xì)胞描述為血液系統(tǒng)的“頂梁柱(heavy lifter)”,。他說，“它們是血細(xì)胞中稱作細(xì)胞因子的激素的作用靶標(biāo),，其中Don Metcalf教授和同事們已經(jīng)證實這些激素在調(diào)節(jié)血細(xì)胞產(chǎn)生中發(fā)揮著關(guān)鍵性作用,。在遭受應(yīng)激如流血時，在感染期間或者接受化療之后,，確實是血祖細(xì)胞通過替換丟失或受損的血細(xì)胞而作出反應(yīng)。”
Kauppi博士說,，研究小組特別對髓樣祖細(xì)胞(myeloid progenitor cell)興趣極大,，因為這種細(xì)胞產(chǎn)生巨核細(xì)胞---一種產(chǎn)生凝血作用的血小板的骨髓細(xì)胞,。她說，“我們使用一套這些祖細(xì)胞特異性的細(xì)胞表面標(biāo)記,，從而允許我們分離和描述這些細(xì)胞,。”
研究人員吃驚地地發(fā)現(xiàn)人們曾認(rèn)為只能產(chǎn)生巨核細(xì)胞的祖細(xì)胞也能夠產(chǎn)生紅細(xì)胞。
Ng博士說,，“我們能夠清晰地證實這些小鼠巨核細(xì)胞祖細(xì)胞在對諸如促血小板生成素(thrombopoietin)和促紅細(xì)胞生成素(erythropoietin)之類的細(xì)胞因子作出反應(yīng)之后產(chǎn)生巨核細(xì)胞或者紅細(xì)胞,，這是非常令人意料之外的。此外,，我們發(fā)現(xiàn)人們以前認(rèn)為只能制造嗜中性細(xì)胞(neutrophil)和單核細(xì)胞的其他祖細(xì)胞群體也能夠制造紅細(xì)胞和血小板,。事實上，我們將不得不重新描繪骨髓中制造紅細(xì)胞和血小板的圖譜,。”
Kauppi博士說,，研究人員發(fā)現(xiàn)他們能夠通過使用不同的細(xì)胞因子組合調(diào)節(jié)血祖細(xì)胞變成巨核細(xì)胞或者紅細(xì)胞。她說,，“如今我們正確地鑒定出主要細(xì)胞并且確定它們?nèi)绾螌ι婕凹t細(xì)胞和血小板產(chǎn)生的細(xì)胞因子信號作出反應(yīng),，這就為人們理解健康時和生病時如何影響這些祖細(xì)胞打下基礎(chǔ)。比如,，我們能夠更好地理解遺傳改變?nèi)绾慰赡軐?dǎo)致某種血液疾病的產(chǎn)生,。”
Ng博士說，這些發(fā)現(xiàn)也將有助于研究人員發(fā)現(xiàn)能夠控制血祖細(xì)胞的新方法,。
Ng博士說,，“這一研究是人們未來開發(fā)出治療血液疾病患者的方法的第一步。當(dāng)細(xì)胞制造過多時,，如骨髓增生性疾病,，人們可能通過限制血細(xì)胞產(chǎn)生來治療疾病，或者當(dāng)血液系統(tǒng)受損時,，如癌癥治療或感染期間,，促進(jìn)血液產(chǎn)生來治療疾病。” (生物谷：towersimper編譯)
延伸閱讀：
Nature：鑒定出產(chǎn)生培育造血干細(xì)胞微環(huán)境的細(xì)胞
Mol. Cell：SENP1蛋白在T細(xì)胞和B細(xì)胞發(fā)育中發(fā)揮關(guān)鍵性作用
Cell：血祖細(xì)胞接受微環(huán)境細(xì)胞和子血細(xì)胞信號維持平衡
Science：細(xì)胞內(nèi)隨機性競爭決定B細(xì)胞命運
Science：揭示B細(xì)胞不均等分裂產(chǎn)生抗體機制
Nat. Genet：發(fā)現(xiàn)造血干細(xì)胞分化關(guān)鍵性基因Dnmt3a
Nat. Genet：Dnmt3a抑制造血干細(xì)胞自我更新基因表達(dá)
Cell Stem Cell：揭示造血干細(xì)胞來源的秘密
Gene Dev.：麻省理工白頭研究所首次發(fā)現(xiàn)長鏈非編碼RNA阻止紅細(xì)胞死亡
doi:10.1073/pnas.1121385109
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Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential
Ashley P. Ng, Maria Kauppi, Donald Metcalf, Ladina Di Rago, Craig D. Hyland, and Warren S. Alexander
Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate the production of precise numbers of mature blood cells of diverse functional lineages. Identification of cell-surface antigen expression associated with hematopoietic lineage restriction has allowed prospective isolation of progenitor cells with defined hematopoietic potential. To clarify further the cellular origins of megakaryocyte commitment, we assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in the adult mouse bone marrow. We show that megakaryocytes arise from CD150+ bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3− fraction of the pregranulocyte-macrophage population. We define a bipotential erythroid-megakaryocyte progenitor population, the CD150+CD9loendoglinlo fraction of Lin−cKit+IL7 receptor alpha−FcγRII/IIIloSca1− cells, which contains the bulk of the megakaryocyte colony-forming capacity of the bone marrow, including bipotential megakaryocyte-erythroid colony-forming capacity, and can generate both erythrocytes and platelets efficiently in vivo. This fraction is distinct from the CD150+CD9hiendoglinlo fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150+CD9loendoglinhi fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that bipotential erythroid-megakaryocyte progenitor and CD150+CD9hiendoglinlo cells are TPO-responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum.
