Research
Cellular states and fates are influenced by the intricate combinatorial interactions between genetic and epigenetic programs. Our research focuses on mapping and characterizing the diverse potency states of stem cells. To achieve this, we have developed advanced tools and platforms capable of tracing and integrating transcriptomic, epigenomic, and epitranscriptomic information, which helps elucidate the mechanisms regulating cell fate transitions. By leveraging these insights, we aim to engineer specific cell fate functionalities through reprogramming and trans-differentiation, ultimately enhancing our understanding of cellular identity and potential (Fig 1).
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Mapping Potency States of Stem Cells:
Embryonic stem cells (ESCs) effectively repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). In our earlier work, we systematically dissected the cellular factors involved in provirus repression in ESCs through a genome-wide siRNA screen (Yang et al, Cell 2015). This investigation revealed that histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i), and chromatin modifiers (Trim28/Eset/Atf7ip) are crucial determinants in establishing provirus and ERV silencing
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Engineering Cell Fate through Reprogramming and Differentiation:
Our previous research in the field of cell fate reprogramming has demonstrated that CD34+ hematopoietic progenitor cells are amenable to rapid reprogramming (Loh et al., Blood 2009). In contrast, while terminally differentiated human T-cells can be reprogrammed, the process takes nearly a month (Loh et al., Cell Stem Cell 2010). Additionally, we showed that by targeting erythroblasts in circulation, it is possible to reprogram human blood cells using just a single drop of blood