最近用小鼠进行的研究工作发现,多能胚胎isl1+(表达Islet 1)祖细胞能够对心脏中所有主要细胞类型做出贡献。人心脏的生成被认为涉及比较多样化的通道。
最近,一组多样化的、具有多能性的人胎儿ISL+心血管祖细胞已在正在发育中的人心脏的右心房及外流血管中被发现。将转基因及基因定向技术应用于人胚胎干细胞系之后发现,这些原始祖细胞在分化成心脏中三大主要细胞类型(心肌细胞、平滑肌和内皮)之前能够自我更新和扩展。这一发现对关于心血管疾病的人类模型的建立、甚至对人类再生医学都有意义。(生物谷Bioon.com)
生物谷推荐原始出处:
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.