How multi-dimensional molecular architecture regulate cell fate decisions during mammalian embryogenesis? The Zhou Lab's long-term goal is to understand how cells regulate the commitment to specific lineage and how failure to execute terminal differentiation can underlie diseases. This understanding of cell fate and embryogenesis is a critical and overlooked facet of the teaching and practice of medicine and the conduct of biomedical research.

Conceptually, the Zhou Lab integrates omics profiling, genetic/epigenetic manipulation, and in vitro/vivo functional identification to link the genome with cumulative cellular phenotypes during embryogenesis. In particular, we are interested in understanding how changes in transcriptome and epigenome coordinate to shape the gene-expression landscape to form functional state of a developmental cell.

Physiologically and developmentally, connecting preceding blastocyst formation and following gastrulation respectively, peri-implantation embryogenesis is a key biological event during mammalian development. The embryo undergoes a series of cellular and molecular regulatory processes from pre- to post-implantation transition (PPT). The Zhou Lab is also interested in molecular transition, lineage specification, embryo patterning, the mother-offspring interaction and implantation activities. Our studies will positively enhance researcher's direct exploration of embryonic development in human beings and benefit reproductive medicine.

1. Employing/developing single-cell multi-omics analysis to uncover the molecular patterns of lineage specialization during embryonic development;
2. Establishing in vitro/vivo models to understand the regulatory mechanism of cell fate transition during embryogenesis from the phenotypic/functional dimension;
3. Exploring the regulatory principles in embryo implantation and tumor evolution in reproductive system.

Molecular and cellular programs along pre- to post-implantation transition (PPT). Early embryonic development undergoes dramatic molecular reprogramming and cellular activities. Upon advances of omics techniques, we now know that cell fate and embryogenesis are subject to networked molecular regulation. Our lab hopes to develop and apply low-input/single-cell multi-dimensional molecular measurement, to observe and mine the molecular and cellular events of peri-implantation development, with the purpose of predicting their potential regulatory functions.

Cell fate during peri-implantation embryogenesis. To further inspire regenerative medicine and curative therapy, integrating high-dimensional data and extracting molecular mechanisms regulating cell fate beyond molecular map is urgently needed. The Zhou Lab aims to combine omics to mine candidate regulators, genetic and epigenetic manipulations, and understand their molecular functions through in vivo/vitro embryonic systems.

Embryo implantation and reproductive tumor progression. Although implantation failure is an important cause of early habitual abortion, little is known about the factors causing embryo implantation failure. Meanwhile, with limited and potentially ethically controversial human embryo samples, we can hardly directly use human embryos to study the molecular mechanisms regulating the early cell fate determinations. We are interested to apply cell lines to reconstruct and evaluate the basic structure and development path of the embryo. Based on the in-depth transcriptome profiling, we can predict the potential key signaling molecules regulating embryo implantation/gastrulation, which are essential clues for optimizing embryo culture and in vitro embryo reconstruction.

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