Generating pure populations of human tissue progenitors
Identifying the extracellular signals that control stem cell differentiation into one cell-type or the other at each lineage branchpoint provided unique insight into how to differentiate stem cells into pure populations of desired lineages. At each pairwise lineage choice, by providing the inductive signals to specify the desired fate while inhibiting signals that otherwise steered differentiation towards the unwanted fate, we could "force" ESCs to differentiate into a highly pure population of a desired cell-type by blocking off alternate paths. Through this approach, we differentiated ESCs into enriched populations of human liver progenitors that could engraft the mouse liver (Loh & Ang et al., 2014; Cell Stem Cell; Ang et al., 2018; Cell Reports) and we also generated human bone progenitors that could form an ectopic human bone in mice (Loh & Chen et al., 2016; Cell).
Our capacity to produce these pure populations of human tissue progenitors therefore provides a foundation for regenerative medicine. With our collaborators, we also are mapping the transcriptional and chromatin landscapes of these human tissue progenitors to illuminate the stepwise molecular events through which pluripotent cells develop into various tissues (Koh & Sinha et al., 2016; Scientific Data).