Project description:In order to study the genomic occupancy of transcription factors, including SOX9, ETV4 and ETV5, in human foetal lung tip progenitor cells, we have introduced Targeted DamID system via lentivirus in a human foetal lung tissue derived organoid culture (Nikolic et al., 2017). We were able to identify the corresponding TF motif enrichment and discovered a potential co-regulation function of SOX9 and ETV factors in human feotal lung progenitor cells. This study has pioneered the use of targeted DamID approach in tissue derived organoid system.
Project description:Gene expression in the human foetal heart for a comparison with cardiomyocytes derived from human pluripotent stem cells. Human foetal heart samples were collected from the individual chambers of the heart at various stages of development. This provided the opportunity to perform gene expression analysis and identify genes involved in the formation of the heart in each of the four chambers and at different stages of development. The dataset can be used to benchmark human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) in terms of their maturation state by comparing it to the foetal heart samples. Two commercially available reference RNA sets are included in the analysis in order to characterize future sets of hPSC-CMs.
Project description:This study is associated with the GEO accession GSE216019. Abstract from article: Re-activating quiescent adult epicardium represents a potential therapeutic approach for human cardiac regeneration. However, the exact molecular differences between inactive adult and active foetal epicardium are not known. Here, we combined foetal and adult human hearts for the first time using single-cell and single-nuclei RNA sequencing, and compared epicardial cells from both stages. We found a migratory fibroblast-like epicardial population only in the foetal heart and foetal epicardium expressed angiogenic gene programs, while the adult epicardium was solely mesothelial and immune-responsive. Furthermore, we predicted that adult hearts may still receive foetal epicardial paracrine communication, including WNT-signalling with endocardium, reinforcing the validity of regenerative strategies that administer or reactivate epicardial cells in situ. Finally, we explained graft efficacy of our human embryonic stem-cell derived epicardium model, by noting its similarity to human foetal epicardium. Overall, our study defines epicardial programs of regenerative angiogenesis absent in adult hearts, contextualises animal studies, and defines epicardial endpoints required for effective human heart regeneration.
Project description:Re-activating quiescent adult epicardium represents a potential therapeutic approach for human cardiac regeneration. However, the exact molecular differences between inactive adult and active foetal epicardium are not known. Here, we combined foetal and adult human hearts for the first time using single-cell and single-nuclei RNA sequencing, and compared epicardial cells from both stages. We found a migratory fibroblast-like epicardial population only in the foetal heart and foetal epicardium expressed angiogenic gene programs, while the adult epicardium was solely mesothelial and immune-responsive. Furthermore, we predicted that adult hearts may still receive foetal epicardial paracrine communication, including WNT-signalling with endocardium, reinforcing the validity of regenerative strategies that administer or reactivate epicardial cells in situ. Finally, we explained graft efficacy of our human embryonic stem-cell derived epicardium model, by noting its similarity to human foetal epicardium. Overall, our study defines epicardial programs of regenerative angiogenesis absent in adult hearts, contextualises animal studies, and defines epicardial states required for effective human heart regeneration.
Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Exiqon miRCURY microarrays. This was compared to profiles from mature human hepatocytes. Foetal LPCs exhibit a distinct miRNA profile consistent with a stem cell signature, cell division, and some liver-specific functions.
