Research
Stem cell research intersects with regenerative medicine, reproduction, cancer therapy, metabolic disorders, and aging in humans and animals. A key challenge is obtaining 'perfect seed stem cells' capable of generating diverse somatic cells efficiently. Through splicing inhibition, we achieved stable culturing of mouse TBLCs (Cell, 2021) and human TBLCs (Cell, 2024). These TBLCs, distinct from ESCs/iPSCs, resemble 2-/4-cell blastomeres and generate embryonic and extraembryonic tissues. Based on this discovery, we're developing a universal medium to reprogram pluripotent stem cells into totipotent ones across species. These cells offer a unique system for studying early embryo development and hold promise for regenerative medicine.
Culturing of embryonic stem cell in vivo
Zygotes and early blastomeres possess totipotency, the highest level of developmental potency, forming both embryonic and extraembryonic tissues. Capturing totipotent stem cells in vitro comparable to in vivo totipotent embryos is challenging. In 2021, our lab achieved a breakthrough by culturing mouse totipotent blastomere-like cells (mTBLC) using splicing inhibition (Shen et al., 2021). Expanding on this, we successfully cultured human totipotent blastomere-like cells (hTBLC) from hESCs and iPSCs (Li et al., 2024).
In the past decade or so, the rapid development of single-cell RNA sequencing(scRNA-seq) technology has changed the research paradigm of embryonic development and disease occurrence. A large amount of work has provided detailed information of cell type landscape and regulatory networks in organs and tissues, while there is still a gap to the actual structure inside organs and tissues. In recent years, a group of spatial transcriptomics technologies have supplemented the spatial localization information of cells on the basis of scRNA-seq, deepening our understanding of tissue structure and accelerating the annotation work of drawing atlas.
Single cell and spatial insight of disease and early embryonic development
Using spatial transcriptomics technology, we have found that abnormal embryonic development may not only come from the abnormalities in the molecular level, but also from the wrong cellular localization, which can lead to dysfunction of cells and disruption of life activities. We hope to use spatial technology to provide new insights and strategies for the treatment of diseases and tumors.
Publications: Cell,2023a Cell,2023b CSC,2022
Cross-species bioengineering
We attempt to reconstitute specific RNA regulatory pathways from plants or microorganisms in animal cells and study their potential applications in translational medicine. Recently, we found that plant immune protein RDR1 can modify AGO2-free microRNA duplexes widely accumulated in cancer cells to regulate global miRNA expression to specifically inhibit tumor proliferation.
Publications: Cell,2022 Life.Med.,2022
Novel RNA regulatory pathways
We are very interested in identifying novel RNA regulatory elements and studying their related regulatory mechanisms, such as ATI-mediated global miRNA dosage control and RBD-mediated transcriptional regulation. Additionally, we are further focused on the role of RNA regulation in the transitions of totipotency and pluripotency in embryonic stem cells, as well as in stem cell differentiation.
Publications: Mol.Cell,2024 Nature,2021