In Vivo Human Somitogenesis Guides Somite Development from hPSCs.
In Vivo Human Somitogenesis Guides Somite Development from hPSCs.
复制标题
DOI：
10.1016/j.celrep.2017.01.040
复制
发表时间：
2017-02-07
期刊：
影响因子：
8.8
通讯作者：
Pyle AD
中科院分区：
文献类型：
--
作者：
Xi H;Fujiwara W;Gonzalez K;Jan M;Liebscher S;Van Handel B;Schenke-Layland K;Pyle AD
体节在胚胎发育过程中形成，并产生独特的细胞和组织类型，如骨骼肌、骨骼和椎骨软骨。利用体细胞发生阶段的人类胚胎，我们对人类分裂前期的中胚层以及新生的和发育的体节进行了转录图谱分析。除了Wnt/β-catenin等保守途径外，我们还发现骨形态发生蛋白和转化生长因子β信号是人类体细胞发生的主要调节因子。这一信息使我们能够开发出一种有效的方案，在体外从人类多能干细胞(HPSCs)中获得体节细胞。重要的是，体外分化细胞逐渐表达在体内体细胞发生过程中已知的不同发育阶段的标记。此外，当受到特定谱系分化条件时，hPSC来源的体节细胞具有多能产生体节衍生物的能力，包括骨骼肌细胞、骨细胞和软骨细胞。这项工作提高了我们对人类体细胞发生的理解，并可能增强我们治疗影响体节素衍生物的疾病的能力。
Somites form during embryonic development and give rise to unique cell and tissue types, such as skeletal muscles and bones and cartilage of the vertebrae. Using somitogenesis stage human embryos, we performed transcriptomic profiling of human presomitic mesoderm as well as nascent and developed somites. In addition to conserved pathways such as WNT/β-catenin, we also identified BMP and TGFβ signaling as major regulators unique to human somitogenesis. This information enabled us to develop an efficient protocol to derive somite cells in vitro from human pluripotent stem cells (hPSCs). Importantly, the in vitro differentiating cells progressively expressed markers of distinct developmental stages known during in vivo somitogenesis. Furthermore, when subjected to lineage-specific differentiation conditions, the hPSC-derived somite cells were multipotent in generating somite derivatives, including skeletal myocytes, osteocytes and chondrocytes. This work improves our understanding of human somitogenesis and may enhance our ability to treat diseases affecting somite derivatives.