關(guān)鍵詞： 胚胎干細(xì)胞 熒光標(biāo)記 肺部祖細(xì)胞 甲狀腺祖細(xì)胞 肺氣腫 囊腫性纖維癥
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鑒于胚胎干細(xì)胞類(lèi)似于早期發(fā)育中的胚胎，美國(guó)波士頓大學(xué)再生醫(yī)學(xué)中心主任Darrell Kotton和同事們?cè)谝豁?xiàng)新研究中研究胚胎發(fā)育過(guò)程中正常的肺部和甲狀腺發(fā)育。以前的研究表明來(lái)自胚胎內(nèi)胚層的祖細(xì)胞(progenitor cell)產(chǎn)生肺部、甲狀腺,、胰腺,、胃腸道和其他器官,。為此，研究人員著重研究胚胎發(fā)育發(fā)生的時(shí)間以便鑒定出哪些因子決定胚胎干細(xì)胞如何分化,。
在這項(xiàng)研究中,，研究人員對(duì)胚胎干細(xì)胞進(jìn)行基因改造使得它們含有一個(gè)熒光標(biāo)記，這樣當(dāng)體外培養(yǎng)的胚胎干細(xì)胞產(chǎn)生肺細(xì)胞或者甲狀腺細(xì)胞時(shí),，這種標(biāo)記發(fā)出熒光,。利用這種方法，研究人員讓胚胎干細(xì)胞分化為內(nèi)胚層細(xì)胞,，然后鑒定誘導(dǎo)肺細(xì)胞系和甲狀腺細(xì)胞系產(chǎn)生的生長(zhǎng)因子,。最終，他們能夠利用每個(gè)起始的胚胎干細(xì)胞產(chǎn)生160個(gè)肺部或者甲狀腺祖細(xì)胞,，而且這些祖細(xì)胞只有當(dāng)它們變成肺細(xì)胞或者甲狀腺細(xì)胞時(shí)熒光標(biāo)記才發(fā)出熒光,，從而能夠?qū)⑺鼈兗兓?/p>
為了證實(shí)研究人員純化的這些細(xì)胞確實(shí)是肺部祖細(xì)胞，Kotton領(lǐng)導(dǎo)的研究小組研究這些細(xì)胞的全局基因表達(dá)譜,，并將它們放置在一個(gè)三維肺部支架(lung scaffold)中,，結(jié)果這些細(xì)胞生長(zhǎng)并發(fā)生增殖，形成兩種類(lèi)型的正常情況下包被肺泡囊(air sac of the lung)的肺細(xì)胞,。
這些研究發(fā)現(xiàn)表明這種技術(shù)能夠被用來(lái)在體外培養(yǎng)原始性肺部祖細(xì)胞以便來(lái)研究人類(lèi)疾病,，從而可能導(dǎo)致人們開(kāi)發(fā)出治療包括肺氣腫(emphysema)和囊腫性纖維癥(Cystic Fibrosis)在內(nèi)的末期肺病的新方法。
歸納在一起,，研究人員在體外利用胚胎干細(xì)胞獲得純的肺部和甲狀腺祖細(xì)胞群體，而且這些細(xì)胞能夠成功地被用來(lái)模擬肺部和甲狀腺組織形成的重要發(fā)育階段,。同時(shí),，研究人員鑒定出胚胎干細(xì)胞分化為肺部祖細(xì)胞所必需的因子。這些研究結(jié)果有助于人們利用組織工程技術(shù)開(kāi)發(fā)出新的基于基因和細(xì)胞的療法來(lái)治療肺部,。相關(guān)研究結(jié)果于2012年4月6日發(fā)表在Cell Stem Cell期刊上,。(生物谷：towersimper編譯)
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doi:10.1016/j.stem.2012.01.019
PMC:
PMID:
Efficient Derivation of Purified Lung and Thyroid Progenitors from Embryonic Stem Cells
Tyler A. Longmire, Laertis Ikonomou, Finn Hawkins, Constantina Christodoulou, Yuxia Cao, J.C. Jean, Letty W. Kwok, Hongmei Mou, Jayaraj Rajagopal, Steven S. Shen, Anne A. Dowton, Maria Serra, Daniel J. Weiss, Michael D. Green, Hans-Willem Snoeck, Maria I. Ramirez, Darrell N. Kotton
Two populations of Nkx2-1+ progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGFβ and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1GFP knockin reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.
