Research direction
The reproductive system is composed of various cells and has complex tissues at different developmental stages. Our long-term goal is to reveal the cell differentiation pathways and molecular mechanisms of reproductive system development, as well as the role of mechanical force signals during this process. To achieve this, we have constructed unique, specifically fluorescently labeled transparent zebrafish, enabling long-term, high-resolution, and deep imaging of the complete process of reproductive system development to maturity in vivo. Single-cell and spatial sequencing techniques are used to study the cell differentiation pathways during reproductive system development and identify key factors. Furthermore, we use embryonic stem cell induction differentiation to construct the reproductive system in vitro, conducting disease simulation related to clinical applications, drug screening, and exploration of pathogenesis and treatment.
Our experimental approaches include advanced microscopic imaging techniques such as line scanning and rotating disk confocal microscopy, two-photon microscopy, optical sectioning microscopy, ultra-high resolution microscopy, fluorescence lifetime imaging, and three-dimensional reconstruction using high-pressure freezing - field emission scanning electron microscopy. We also combine various image analysis methods such as ImageJ, ilastik (machine learning), Imaris (three-dimensional imaging analysis), and Matlab (custom image processing). At the same time, we apply molecular biology and biophysics experimental methods to explore the mysteries of follicular tissue morphology formation. Furthermore, during this process, we will seek new mechanisms for mechanical force regulating cell fate and tissue morphology establishment.
Project Case: Single-cell Differentiation Mediated by Mechanical Lateral Inhibition.
Lateral inhibition is an important mechanism that mediates cell differentiation and tissue morphogenesis. The typical lateral inhibition is accomplished through the Delta-Notch signaling pathway, but it is not clear whether this is the only way for lateral inhibition. Through our research, we discovered that in the early stage of zebrafish follicle development, the transcriptional co-activator factor TAZ activity increased and aggregated in the nucleus of a small cluster of granular cells located at the animal pole of the oocyte. The activity of TAZ in one of these cells continuously enhanced and gradually increased, thereby mechanically squeezing the surrounding cells and inhibiting the TAZ activity of these cells through mechanical signal transduction, ultimately achieving the differentiation of a single cell into an embryonic pore precursor cell. When using capillary suction to extract the animal pole of the follicle or using laser to cut the embryonic pore precursor cells and releasing the compressed state of the surrounding cells, these cells will rapidly increase their TAZ activity and can re-differentiate into embryonic pore precursor cells. Our discovery reveals a new mode of mechanical force regulating cell fate and proposes and proves the mechanical lateral inhibition theory.