多能性因子调控细胞间信号通讯诱导猪胚胎干细胞分化的分子机制

Porcine embryonic stem cells have tremendous application prospects and values in breed of pig variety and human regenerative medicine. But there are still so many difficulties and obstacles in research of porcine embryonic stem cells. Rapidly spontaneous differentiation has been considered as the most serious problem should be solved. The mechanism of differentiation induced is still far from clear now, and the researching reported definitively in this issue is very rare, even in the embryonic stem cell of mouse. The intercellular signal communication is an important mechanism in the embryonic development to regulate cells differentiation and three embryonic germ layer formation. But this issue was rarely mentioned in the past reports about embryonic stem cells researching. The signal pathway of some secretory proteins of one cell to their receptors on the surface of another cell would be the main context of intercellular signal communication among embryonic stem cell neighbors. And this intercellular signal communication would be with a differentiation inducing genius, for to form a microenvironment is very favorable to maintain pluripotency of an embryonic stem cell. Here a hypothesis was presented that the intercellular signal communication of secretory proteins and receptors inducing differentiation neighboring embryonic stem cells would be the dynamics of embryonic stem cells spontaneous differentiation. The expression of these secretory proteins, which was secreted form an embryonic stem cell to induce its neighbor’s differentiation, would be increased by pluripotency factors in this hypothesis which, however, were considered as differentiation inhibition force in past reports. To demonstrate this hypothesis, the pathway of differentiation inducing proteins and their receptors in embryonic stem cells neighborhood signal communication, whose expression were suppose to be regulated by pluripotency factors, were researched at molecular, cell, and embryonic levels to explore the mechanism by which pluripotency regulating porcine embryonic stem cells signal communication. And a new mechanism of porcine embryonic stem cells spontaneous differentiation would be presented based on this hypothesis.

猪胚胎干细胞在品种培育和再生医学等方面均具有广阔的应用前景，但目前的研究还面临许多困难和障碍。快速自发分化是猪胚胎干细胞多能性维持需要解决的主要问题。但即使在小鼠胚胎干细胞的研究中，对自发分化的分子机制目前仍尚无确切报道。细胞间信号通讯是胚胎发育过程中调控细胞分化和三胚层形成的重要机制，但以往胚胎干细胞的研究中却尚未涉及。诱导邻近细胞分化的分泌蛋白及其受体可能是胚胎干细胞间信号通讯的主要内容，以形成对信号释放细胞多能性维持有利的微环境。这种诱导邻近细胞分化的信号通讯可能是胚胎干细胞自发分化的主要动因。通过调控分泌蛋白及其受体的表达，多能性因子可引起诱导邻近细胞分化的细胞间信号通讯。为验证这一假说，本研究拟从分子、细胞、和胚胎的层面，对多能性因子调控分化诱导的分泌蛋白及受体表达的信号通路深入研究，明确多能性因子调控猪胚胎干细胞间信号通讯的分子机制，提出猪胚胎干细胞自发分化产生的新机制。