Abstract: Previous reports suggest that hypoblasts acquire plasticity in their cell fate through epigenetic remodeling. To date, however, whether human hypoblasts contributed to other cell types than yolk sac endoderm, whether hypoblasts are transient cell populations or contribute to embryo part is unclear. Even more important, how hypoblast cell fate is epigenetically regulated through the interaction with other embryonic tissues is also unknown. Based on our preliminary data and previous observations in stem cell-derived embryo models and human embryos, we hypothesize that hypoblast might directly contribute to hematopoietic lineage by opening the loci of hematopoietic programs. To investigate the hypothesis, we use novel molecular barcoding system and computational methods to determine the lineage of hypoblast in stem cell-derived embryo models with expressive barcodes and cross-comparison with human and non-human primate embryos. We also investigate the epigenetic regulation of hypoblast cell fate which provide insights into how to instruct their lineage by forced expression of transcription factors. Besides deepening our knowledge of human embryonic development, these insights will help us to understand how to derive functional cells from human stem cells for cell therapy, disease modeling, and drug discovery.
