近日,，中國科學(xué)院廣州生物醫(yī)藥與健康研究院陳永龍研究組與香港中文大學(xué)趙暉研究組合作,，借助通過基因芯片篩選獲得的首個腹部胰腺前體細(xì)胞特異表達的標(biāo)記基因vpp1，在非洲爪蛙胚胎中發(fā)現(xiàn)轉(zhuǎn)錄因子hhex決定腹部胰腺前體細(xì)胞的形成,。
過表達單一轉(zhuǎn)錄因子hhex足以將大量將來形成腸道的內(nèi)胚層細(xì)胞轉(zhuǎn)變?yōu)関pp1陽性的腹部胰腺前體細(xì)胞,，進而在爪蛙蝌蚪中形成一個巨大的胰腺，其中成熟的,、合成胰島素的胰島β細(xì)胞的發(fā)育與正常胰腺中的完全相同,。反之，hhex敲減后,，vpp1陽性細(xì)胞急劇減少,，最終導(dǎo)致腹部胰腺的缺失。該成果近日在《美國國家科學(xué)院院刊》（PNAS）在線發(fā)表,。
闡明從受精卵發(fā)育開始到各種不同組織器官的細(xì)胞譜系的建立過程,，是進行干細(xì)胞定向誘導(dǎo)分化并最終將其推向臨床應(yīng)用的基礎(chǔ),。該研究揭示了預(yù)定形成腹部胰腺前體細(xì)胞的命運決定。在原腸作用期間,，hhex與vpp1的表達有部分重疊,，非重疊部分的hhex陽性細(xì)胞主要是預(yù)定形成肝臟的前體細(xì)胞，目前還不清楚為什么在爪蛙胚胎中過表達hhex只能選擇性地誘導(dǎo)形成巨大的腹部胰腺而不能使肝臟增大,。研究人員希望更進一步的研究可以闡明來源于內(nèi)胚層的不同類型細(xì)胞譜系的建立和命運決定的機制,，為干細(xì)胞的定向誘導(dǎo)分化（如胰島β細(xì)胞的分化）和應(yīng)用奠定基礎(chǔ)。
該項研究受到科技部973項目和中科院項目百人計劃資助,。（生物谷Bioon.com）
doi:10.1073/pnas.1206547109
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Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos
Hui Zhaoa,1, Dandan Hanb,c,1, Igor B. Dawidd,2, Tomas Pielere,2, and Yonglong Chenb,2
Liver and ventral pancreas develop from neighboring territories within the endoderm of gastrulae. ventral pancreatic precursor 1 (vpp1) is a marker gene that is differentially expressed in a cell population within the dorsal endoderm in a pattern partially overlapping with that of hematopoietically expressed homeobox (hhex) during gastrulation. In tail bud embryos, vpp1 expression specifically demarcates two ventral pancreatic buds, whereas hhex expression is mainly restricted to the liver diverticulum. Ectopic expression of a critical dose of hhex led to a greatly enlarged vpp1-positive domain and, subsequently, to the formation of giant ventral pancreata, putatively by conversion of intestinal to ventral pancreatic precursor cells. Conversely, antisense morpholino oligonucleotide-mediated knockdown of hhex resulted in a down-regulation of vpp1 expression and a specific loss of the ventral pancreas. Furthermore, titration of hhex with a dexamethasone-inducible hhex-VP16GR fusion construct suggested that endogenous hhex activity during gastrulation is essential for the formation of ventral pancreatic progenitor cells. These observations suggest that, beyond its role in liver development, hhex controls specification of a vpp1-positive endodermal cell population during gastrulation that is required for the formation of the ventral pancreas.
