Graduate Student Seoul National University, Republic of Korea
Abstract: Lineage specification during early embryo development results in the formation of the pluripotent cell population, known as inner cell mass (ICM), and the ICM has the potential to generate three germ layers of endoderm, mesoderm, and ectoderm during gastrulation. Embryonic stem cells (ESCs) can recapitulate early embryogenesis in vitro and differentiate into various cell types derived from all three germ layers, making them widely used in developmental biology research. The generation of multiple mesodermal derivatives including cardiovascular, hematopoietic, and mesenchymal cells from ESCs is well demonstrated in human and mouse. However, since ESCs of pig have been established relatively recently, studies of their direct differentiation through the modulation of signaling pathways are limited. Therefore, we elucidated the signaling pathways involved in the mesodermal differentiation of pig ESCs and optimized the differentiation protocol for inducing pig ESCs into the mesodermal lineage. Transcriptional expression levels of mesodermal markers were significantly upregulated in pig ESCs treated with a combination of signaling molecules, compared with non-treated pig ESCs. In addition, this treatment did not enhance the transcript levels of endodermal and ectodermal markers. Interestingly, a certain signaling molecule reported to be associated with mesodermal differentiation of human ESCs had no effect on pig ESCs, indicating species-specific characteristics of pigs. Taken together, we efficiently derived mesodermal progenitors from pig ESCs by modulating signaling pathways related to mesodermal lineage development. Because ESCs are capable of unlimited self-renewal, these progenitors can be employed as a stable cell source for the production of various mesodermal derivatives. Especially, ESCs are known to pass through intermediate stages such as the mesoderm during differentiation into mesenchymal stem cells (MSCs), and thus these progenitors can be utilized for establishing MSCs derived from ESCs. Therefore, as part of further studies, we are preparing to induce mesodermal progenitors into MSCs and dissect the mechanisms thereof.
Funding Source: This work was supported by the BK21 Four program, the Korea Evaluation Institute of Industrial Technology (KEIT) [20012411]; and the National Research Foundation of Korea (NRF) grant [2023R1A2C1005026].
