近日，來自丹麥哥本哈根大學和哈格多恩研究所干細胞中心（DanStem）的科學家們在控制身體胰島素產(chǎn)生的信號路徑上有了新的突破,。研究人員將干細胞轉化產(chǎn)生胰島素的β細胞,，β細胞可以植入到需要它們的病人體內(nèi)。相關研究論文發(fā)表在新一期PNAS雜志上,。
胰島素是由胰腺中的β細胞產(chǎn)生的一種激素,。如果這些β細胞有缺陷的話，機體會發(fā)展有糖尿病,。糖尿病患者往往通過每天注射胰島素來維持血糖,，胰島素是至關重要的?？茖W家們希望,，在不那么遙遠的未來，這項研究發(fā)現(xiàn)將有可能更有效地治療糖尿病,，為糖尿病患者提供新的運作良好的β細胞,，以防止繼發(fā)性疾病如心臟病、失明,、神經(jīng)及腎臟并發(fā)癥的發(fā)生,。
Palle Serup教授解釋說：“為了讓干細胞發(fā)展成胰島素生產(chǎn)β細胞，有必要知道在胎兒的發(fā)育過程中是什么信號機制控制并創(chuàng)造β細胞,。我們新的研究成果能”,。
教授Serup表示：當我們知道具體信號途徑時，我們可以在試管中進行復制,，從而及時將干細胞轉換成β細胞,。
控制干細胞發(fā)展成β細胞的信號途徑的第一步老早就被科學家所知。該研究發(fā)現(xiàn)Notch信號通路培育的干細胞更有效地轉換成產(chǎn)生胰島素的β細胞非常重要,。這項新的研究為下一步的細胞的發(fā)展以及細胞之間溝通的信號鋪平道路,， 這還是個沒有被廣泛認知的領域知識,。（生物谷：Bioon.com）
doi:10.1073/pnas.1203605109
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Mind bomb 1 is required for pancreatic β-cell formation
Signe Horna, Sune Kobberupa, Mark Kalisza, Tino Kleina, Ryoichiro Kageyamab, et al.
During early pancreatic development, Notch signaling represses differentiation of endocrine cells and promotes proliferation of Nkx6-1+Ptf1a+ multipotent progenitor cells (MPCs). Later, antagonistic interactions between Nkx6 transcription factors and Ptf1a function to segregate MPCs into distal Nkx6-1−Ptf1a+ acinar progenitors and proximal Nkx6-1+Ptf1a− duct and β-cell progenitors. Distal cells are initially multipotent, but evolve into unipotent, acinar cell progenitors. Conversely, proximal cells are bipotent and give rise to duct cells and late-born endocrine cells, including the insulin producing β-cells. However, signals that regulate proximodistal (P-D) patterning and thus formation of β-cell progenitors are unknown. Here we show that Mind bomb 1 (Mib1) is required for correct P-D patterning of the developing pancreas and β-cell formation. We found that endoderm-specific inactivation of Mib1 caused a loss of Nkx6-1+Ptf1a− and Hnf1β+ cells and a corresponding loss of Neurog3+ endocrine progenitors and β-cells. An accompanying increase in Nkx6-1−Ptf1a+ and amylase+ cells, occupying the proximal domain, suggests that proximal cells adopt a distal fate in the absence of Mib1 activity. Impeding Notch-mediated transcriptional activation by conditional expression of dominant negative Mastermind-like 1 (Maml1) resulted in a similarly distorted P-D patterning and suppressed β-cell formation, as did conditional inactivation of the Notch target gene Hes1. Our results reveal iterative use of Notch in pancreatic development to ensure correct P-D patterning and adequate β-cell formation.
