多能性幹細胞の分化過程における染色体の機能的構造変化

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My research project investigated the cellular events involved in the differentiation of human embryonic stem (hES) cells into a specialized type of cell called a trophoblast cell. The major part of the project was centered on understanding how chromatin (the architecture of the nucleus) changes when hES cells loose their pluripotency and differentiate into the specialized trophoblast cells. I specifically studied proteins called 'histones' which are the basic unit of chromatin. I was particularly interested in a type of histone protein called 'histone 2A variant Z' (H2AZ). I was interested in H2AZ because it can have different effects on the chromatin architecture when by becoming modified. These modifications primarily concern the addition of small molecules called "acetylation" or "methylation". To study the changes in the modification of H2AZ I used a technique called immunofluorencese (to fluorescently label the proteins or RNA molecules I want to study) I then imaged the cell nucleus with a very sensitive microscope and then perform a specialized type of image processing and analysis that was writen in my laboratory on the captured image. Using these techniques, I found that status of H2AZ acetylation in the stem cell changes very quickly (in as little as 12 hours) following treatment to induce differentiation. I have studied the protein complexes that both acetylate and de-acetylate H2AZ under hES differentiation and found that de-acetylation of H2AZ is critical for differentiation to proceed.