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.

Public Health Relevance

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 my research is to understand the mechanisms that contribute to pluripotency and cell fate specification, using zebrafish as an in vivo model system.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Career Transition Award (K99)
Project #
5K99HD067220-02
Application #
8259145
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Ravindranath, Neelakanta
Project Start
2011-04-20
Project End
2012-04-30
Budget Start
2012-04-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$7,679
Indirect Cost
$569
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Zhang, Yong; Vastenhouw, Nadine L; Feng, Jianxing et al. (2014) Canonical nucleosome organization at promoters forms during genome activation. Genome Res 24:260-6
Vastenhouw, Nadine L; Schier, Alexander F (2012) Bivalent histone modifications in early embryogenesis. Curr Opin Cell Biol 24:374-86