造血干細(xì)胞能制造所有類型的血液細(xì)胞。但是,，究竟是哪些因素影響著一個(gè)特定細(xì)胞類型的產(chǎn)生呢？到目前為止,，人們都認(rèn)為這是一個(gè)隨機(jī)的過程,。法國(guó)國(guó)家科學(xué)研究中心和法國(guó)醫(yī)學(xué)研究所的研究人員最近發(fā)現(xiàn)了決定這些特定細(xì)胞產(chǎn)生的因子，并已在小鼠身上得到驗(yàn)證，此機(jī)制涉及一個(gè)細(xì)胞內(nèi)在因子和一個(gè)外來因子,。相關(guān)研究結(jié)果發(fā)表在近期出版的《細(xì)胞》（Cell）雜志上,。
干細(xì)胞研究成為諸多醫(yī)學(xué)研究的希望之門，要?dú)w功于其能產(chǎn)生體內(nèi)任何細(xì)胞類型或器官的獨(dú)特能力,?？茖W(xué)家們一直在致力于了解干細(xì)胞向特定細(xì)胞分化的機(jī)制。
法國(guó)研究人員一直在對(duì)小鼠造血干細(xì)胞進(jìn)行研究,，其研究重點(diǎn)為骨髓細(xì)胞的發(fā)育,，骨髓細(xì)胞屬白血細(xì)胞譜系，其能通過釋放毒素或?qū)ζ渌囟庖呒?xì)胞發(fā)出警告以同那些吞噬它們的微生物進(jìn)行抗?fàn)?。到目前為止,，從造血干?xì)胞產(chǎn)生不同的特定細(xì)胞被認(rèn)為是一個(gè)隨機(jī)過程。法國(guó)研究人員卻發(fā)現(xiàn),，在骨髓細(xì)胞這個(gè)研究案例中,，有兩種相關(guān)蛋白是聯(lián)合行動(dòng)的，一種蛋白是位于細(xì)胞內(nèi)的轉(zhuǎn)錄因子（transcription factor）,，另一種蛋白則是位于細(xì)胞外的細(xì)胞因子（cytokine）,。
轉(zhuǎn)錄因子能打開或關(guān)閉基因，而一個(gè)細(xì)胞的“身份”則是其擁有的活躍基因的組合體,。正因?yàn)槿绱?，科學(xué)家們懷疑轉(zhuǎn)錄因子對(duì)分化方向起著重要作用?？茖W(xué)家們還了解到,，血液細(xì)胞只能在含有特定細(xì)胞因子（每種細(xì)胞類型的特定荷爾蒙）的環(huán)境中才能繁盛。但到目前為止,，科學(xué)家們都認(rèn)為細(xì)胞因子只是協(xié)助細(xì)胞的生存和再生,，卻不會(huì)影響其“命運(yùn)”。
法國(guó)研究人員則發(fā)現(xiàn),，一個(gè)特定細(xì)胞因子（M-CSF）將干細(xì)胞引向了一條“骨髓路徑”,，如果細(xì)胞內(nèi)的某種轉(zhuǎn)移因子（MafB）水平較低，那么這些干細(xì)胞就只能沿此路徑分化,。此項(xiàng)發(fā)現(xiàn)有助于揭開專業(yè)人員在過去50年來癡迷追尋的秘密,。從長(zhǎng)遠(yuǎn)來看，這些研究成果為找到白血病的形成機(jī)制帶來了曙光,，在白血病中,，不正常的干細(xì)胞仍然是個(gè)懸案，仍能逃脫各種治療方案,。此項(xiàng)研究也為揭示干細(xì)胞如何在大腦,、肌肉或腸道中發(fā)揮作用提供了可借鑒的信息,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 138, Issue 2, 300-313, 23 July 2009 doi:10.1016/j.cell.2009.04.057
MafB Restricts M-CSF-Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells
Sandrine Sarrazin1,2,3,Noushine Mossadegh-Keller1,2,3,9,Taro Fukao1,2,3,5,9,Athar Aziz1,2,3,6,Frederic Mourcin1,2,3,7,Laurent Vanhille1,2,3,Louise Kelly Modis1,2,3,8,Philippe Kastner4,Susan Chan4,Estelle Duprez1,2,3,Claas Otto1,2,3andMichael H. Sieweke1,2,3,,
1 Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France
2 Institut National de la Santé et de la Recherche Médicale (INSERM), U631, Marseille, France
3 Centre National de la Recherche Scientifique (CNRS), UMR6102, Marseille, France
4 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg F-67000, France
5 Present address: Max-Planck Institute of Immunobiology, Stübeweg 51, D-79108 Freiburg, Germany
6 Present address: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
7 Present address: INSERM U917, Faculté de Médecine, Université de Rennes, Rennes F-35043, France
8 Present address: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
9 These authors contributed equally to this work
While hematopoietic stem cell (HSC) self-renewal is well studied, it remains unknown whether distinct control mechanisms enable HSC divisions that generate progeny cells with specific lineage bias. Here, we report that the monocytic transcription factor MafB specifically restricts the ability of M-CSF to instruct myeloid commitment divisions in HSCs. MafB deficiency specifically enhanced sensitivity to M-CSF and caused activation of the myeloid master-regulator PU.1 in HSCs in vivo. Single-cell analysis revealed that reduced MafB levels enabled M-CSF to instruct divisions producing asymmetric daughter pairs with one PU.1+ cell. As a consequence, MafB HSCs showed a PU.1 and M-CSF receptor-dependent competitive repopulation advantage specifically in the myelomonocytic, but not T lymphoid or erythroid, compartment. Lineage-biased repopulation advantage was progressive, maintained long term, and serially transplantable. Together, this indicates that an integrated transcription factor/cytokine circuit can control the rate of specific HSC commitment divisions without compromising other lineages or self-renewal.
