Epigenetics refers to effects on gene expression or function that are inheritable through mitosis or meiosis without altering the primary DNA sequences. Epigenetic mechanisms play important roles in regulating cell identity and activity. Failure to appropriately regulate epigenetic activity leads to abnormal behavior of cells, which underlies many diseases such as diabetes, muscular dystrophy, neurodegenerative disease, infertility, and many forms of cancer. One important, yet poorly understood aspect of epigenetics is how epigenetic information is partitioned in asymmetrically dividing adult stem cells. Many types of stem cells undergo asymmetric cell divisions to give rise to two daughter cells with distinct cell fates: a self-renewed stem cell and a differentiating daughter cell. We found that during the asymmetric division of Drosophila male germline stem cells (GSCs), the preexisting histone 3 (H3) are selectively segregated to the GSC whereas newly synthesized H3 are enriched in the differentiating daughter cell1. Our studies provide the first direct evidence that stem cells retain preexisting histones during asymmetric cell divisions in vivo, which may contribute to maintain their unique epigenetic memory. These unprecedented discoveries have placed us at a unique position to solve a long-standing question regarding whether and how cells maintain their epigenetic memories through many cell divisions and across generations. We propose to use molecular genetics, cell biology, genomic, and biophysical approaches in our research, which will have far-reaching impact on a broad range of fields, including stem cell biology, chromatin biology, developmental biology, and reproductive biology.
An adult human being has approximately 100,000 billion cells comprised of more than 200 cell types, which all originate from a single cell?a fertilized egg. Therefore, a fundamental question to understanding any complex living organism is how cells become different while faithfully maintaining the same genetic material. In this project we plan to systematically study how epigenetic information is established and partitioned into daughter cells, which will have broad impaction on stem cell biology, developmental biology, chromatin biology, and regenerative medicine.
