近日,,美國(guó)與德國(guó)科學(xué)家宣布成功利用人體多功能干細(xì)胞高效地培育出白色脂肪細(xì)胞和褐色脂肪細(xì)胞這兩種人體脂肪生成細(xì)胞,,相關(guān)報(bào)告在線發(fā)表于本周的《自然—細(xì)胞生物學(xué)》(Nature Cell Biology)上,。這項(xiàng)研究為褐色脂肪組織活性相關(guān)治療提供了潛在可能,,從而降低體質(zhì)指數(shù)(BMI)。
目前,,疾病研究所需的人體多功能干細(xì)胞的來源有兩種:人體胚胎和直接用成體細(xì)胞重編程,??茖W(xué)家需要一種高效實(shí)現(xiàn)多功能干細(xì)胞各種分化的方法。此外,,要從其他來源獲取上述兩種脂肪細(xì)胞,,現(xiàn)有的方法也并不理想。在這項(xiàng)研究中,,Chad Cowan和同事以多功能干細(xì)胞為來源,,通過表達(dá)脂肪誘導(dǎo)相關(guān)因子,將近90%的多功能干細(xì)胞分化成為白色和褐色脂肪細(xì)胞,。所獲得的細(xì)胞具有脂類代謝,、胰島素反應(yīng)性等成熟功能,將這些細(xì)胞植入小鼠體內(nèi)后,,其會(huì)發(fā)生異位脂肪沉積,從而形成白色與褐色脂肪組織,。
該項(xiàng)研究成果將直接有助于針對(duì)肥胖以及其他脂肪細(xì)胞相關(guān)癥狀的研究,。(生物谷Bioon.com)
doi:10.1038/ncb2411
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Programming human pluripotent stem cells into white and brown adipocytes
Tim Ahfeldt, Robert T. Schinzel, Youn-Kyoung Lee,David Hendrickson, Adam Kaplan, David H. Lum, Raymond Camahort, Fang Xia, Jennifer Shay, Eugene P. Rhee, Clary B. Clish, Rahul C. Deo,Tony Shen, Frank H. Lau, Alicia Cowley, Greg Mowrer, Heba Al-Siddiqi, Matthias Nahrendorf, Kiran Musunuru, Robert E. Gerszten, John L. Rinn1, & Chad A. Cowan
The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%–90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.