The Role of Chromatin in Pluripotency and Cell Fate Specification

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (Provided by Applicant): Pluripotent cells can differentiate into nearly all cell types and therefore hold great promise for medical applications. The molecular basis for pluripotency, however, is poorly understood. Cell culture studies have generated potential mechanisms for the establishment and maintenance of pluripotency, but the in vivo relevance of these models is largely unclear. The goal of the candidate's research is to understand the interplay among chromatin, pluripotency, and cell fate specification, using zebrafish as an in vivo model system. The candidate previously discovered that there is a characteristic chromatin profile for embryonic pluripotency and that this profile is established during the maternal-zygotic transition. Though her studies have begun to clarify the relationship between chromatin state and pluripotency in vivo, several key questions remain: 1) How does pluripotent chromatin marks change during cell fate specification? 2) What is the role of this chromatin profile in zygotic genome activation and embryonic pluripotency? 3) What directs the establishment of the pluripotent chromatin marks in the embryo? These questions form the basis for the candidate's research plan. The results of the proposed studies will improve our understanding of pluripotency and cell fate decisions in a developmental context. While fundamental in nature, these studies may also inform strategies to more efficiently reprogram and differentiate cells in vitro, one of the major goals of regenerative medicine. NARRATIVE: Pluripotent cells can differentiate into nearly all cell types, and therefore hold great promise for medical applications. The molecular basis for pluripotency, however, is still poorly understood. The goal of the proposed research is to understand the mechanisms that contribute to pluripotency and cell fate specification, using zebrafish as an in vivo model system.