最近用小鼠進(jìn)行的研究工作發(fā)現(xiàn),,多能胚胎isl1+(表達(dá)Islet 1)祖細(xì)胞能夠?qū)π呐K中所有主要細(xì)胞類型做出貢獻(xiàn),。人心臟的生成被認(rèn)為涉及比較多樣化的通道。
最近,,一組多樣化的、具有多能性的人胎兒ISL+心血管祖細(xì)胞已在正在發(fā)育中的人心臟的右心房及外流血管中被發(fā)現(xiàn)。將轉(zhuǎn)基因及基因定向技術(shù)應(yīng)用于人胚胎干細(xì)胞系之后發(fā)現(xiàn),,這些原始祖細(xì)胞在分化成心臟中三大主要細(xì)胞類型(心肌細(xì)胞、平滑肌和內(nèi)皮)之前能夠自我更新和擴(kuò)展,。這一發(fā)現(xiàn)對(duì)關(guān)于心血管疾病的人類模型的建立,、甚至對(duì)人類再生醫(yī)學(xué)都有意義。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 460, 113-117 (2 July 2009) | doi:10.1038/nature08191
Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
Lei Bu1,2,4, Xin Jiang1,2,4, Silvia Martin-Puig1,2, Leslie Caron1,2, Shenjun Zhu1, Ying Shao1, Drucilla J. Roberts3, Paul L. Huang1, Ibrahim J. Domian1,2 & Kenneth R. Chien1,2
1 Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3208, 185 Cambridge Street, Boston, Massachusetts 02114, USA
2 Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA
3 Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
4 These authors contributed equally to this work.
The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential1, 2, 3, 4. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart5, 6, 7, 8. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1+ cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1+ primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.