转录因子TRF3在人胚胎干细胞中内胚层分化中的功能与调控机制研究

Transcription factors play a very important role in germ decision during human embryo development. But the regulation mechanism is still limited understanding. TRF3 (TBP related factor-3) is a recently discovered homologous gene of TBP which is a general transcription factor. TRF3 is involved in hematopoietic differentiation of mice and zebrafish. Due to species differences, the development regulation mechanism of human is more complicated than the model organism. The role of TRF3 in human development, especially in the early fate decision, is still unknown. We found that TRF3 is expressed in the mesendoderm differentiation of human embryonic stem cells, and down-regulation of TRF3 inhibits the mesendoderm differentiation. Therefore, we hypothesized that TRF3 may be involved in the regulation of mesendoderm fate decision. We use human embryonic stem cells as a research model to define the function and molecular mechanism of TRF3 in the mesendoderm differentiation using the methods of molecular biology. cell biology and bioinformatics.The purpose of our study is to reveal the downstream target genes and the interaction factors and to elucidate the molecular mechanism of the regulation of TRF3. Our study will be very important for understanding the fate decision of mesendoderm during human embryo early development.

在人类胚胎发育早期胚层命运决定中，转录因子起着重要的调控作用，但是对于其调控机制仍了解有限。TRF3（TBP related factor-3）是新近发现的通用转录因子TBP的同源基因，小鼠和斑马鱼的研究显示TRF3参与造血分化的调控，由于种属差异性，人类发育调控机制远比模式生物要复杂精密，TRF3在人类发育中特别是在胚层命运决定中的功能仍不清楚。我们新近发现TRF3在人胚胎干细胞的中内胚层分化进程中有表达，TRF3下调抑制中内胚层分化。因此我们推测TRF3可能参与中内胚层命运决定的调控。为明确TRF3的功能与分子机制，本项目拟采用人胚胎干细胞为体外分化模型，结合分子生物学，细胞生物学和生物信息学手段来研究明确TRF3在中内胚层命运决定中的功能，揭示其下游靶基因及相互作用因子，阐明其调控中内胚层分化的分子机制。研究发现对深化人类胚胎发育早期中内胚层命运决定的认识有重要意义。

在人类胚胎发育早期胚层命运决定中，转录因子起着重要的调控作用，但是对于其调控机制仍了解有限。TRF3（TBP related factor-3）是通用转录因子TBP的同源基因，小鼠和斑马鱼的研究显示TRF3参与造血分化的调控，由于种属差异性，人类发育调控机制远比模式生物要复杂精密，TRF3在人类发育中特别是在胚层命运决定中的功能并不清楚。我们通过研究发现TRF3在人胚胎干细胞的中内胚层分化进程中表达，通过crispr-cas9技术敲除TRF3抑制了人胚胎干细胞的中内胚层分化，通过免疫共沉淀与质谱实验我们鉴定了一系列与TRF3相互作用的蛋白因子。该研究明确了TRF3的功能与分子机制，初步阐明了其调控中内胚层分化的分子机制。研究发现对深化人类胚胎发育早期中内胚层命运决定的认识有重要意义。

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