In our lab

We are interested in mechanisms of cell fate decisions in the early mouse embryo and their application to the maintenance and differentiation of embryo-derived stem cells.

We combine tools of genetic manipulation, live imaging, proteomics and single cell expression analysis to explore the fundamental aspects of lineage development. For example, we are investigating epigenetic and regulatory differences between pluripotency and the extraembryonic stem cell state, since this is the key switch that marks loss of totipotency. We are also applying our developmental knowledge to the differentiation of human iPS cells into cell types suitable for exploring new aspects of human biology and disease.

We recently developed a CRISPR/Cas9-based genome editing method that allows for highly efficient, precise insertion of large DNA fragments into the mouse embryo genome. Two-cell homologous recombination (2C-HR)-CRISPR, is based on introducing CRISPR reagents into embryos at the two-cell stage, taking advantage of the open chromatin structure and the likely increase in homologous-recombination efficiency during the long G2 phase. We are currently exploiting this method to generate a number of mouse lines carrying fluorescent reporters, inducible protein degradation systems, optogenetic constructs and other synthetic biology tools.

Current research

Embryo PictureUtilization of Preimplantation embryos is a fundamental system, which allows us to study embryo development in vivo. Our research focuses on characterizing embryo development and understanding the underlying molecular mechanisms of cell fate determination.

Embryo Projects

Stem Cells growing in a plateWe utilize a variety of embryo derived stem cell lines to model lineage establishment in vitro. We study the maintenance of pluripotency as well as cell fate changes through driving differentiation and cell conversion.

Stem Cell Projects

Recent publications

Efficient Generation of Large-Fragment Knock-In Mouse Models Using 2-Cell (2C)-Homologous Recombination (HR)-CRISPR. Gu B, et al., Current Protocols in Mouse Biology. 2020 Mar;10(1).

Esrrb function is required for proper primordial germ cell development in presomite stage mouse embryos. Okamura Eet al., Developmental Biology. 2019 Nov 15;455(2):382-392.

Inhibition of Phosphoinositide-3-Kinase Signaling Promotes the Stem Cell State of Trophoblast. Lee CQE et al., Stem Cells. 2019 Oct;37(10):1307-1318.

Conversion of human and mouse fibroblasts into lung-like epithelial cells. Wong AP et al., Science Reports. 2019 Jun 21;9(1):9027.

Genetic control of early cell lineages in the mammalian embryo. Rossant J. Annual Review of Genetics. 2018 Nov 23;52:185-201.

Gene editing in human development: ethical concerns and practical applications. Rossant J. Development. 2018 Jul 25;145(16).

Efficient generation of targeted large insertions by microinjection into two-cell-stage mouse embryos. Gu B, et al., Nature Biotechnology. 2018 Aug;36(7):632-637.

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Our work