Project description:Gene expression is highly dynamic during fetal development and determines tissue specification and function. In humans, the transcriptional profile of different organs during development has not been systematically studied. However, understanding how a particular tissue acquires its tissue identity will give insight into the development and maturation of tissues from a developmental biology perspective. Next-generation sequencing (DeepSAGE) dataset of 111 RNA samples representing 21 different human fetal organs and the maternal endometrium at three timepoints (gestational ages) during first and second trimester development (W9, W16-18, W22)
Project description:Gene expression is highly dynamic during fetal development and determines tissue specification and function. In humans, the transcriptional profile of different organs during development has not been systematically studied. However, understanding how a particular tissue acquires its tissue identity will give insight into the development and maturation of tissues from a developmental biology perspective.
Project description:While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease states alter the function of the lungs, studies in human lung models are important. Here, we sequenced >150,000 single single-cells from 19 healthy human fetal lung tissues from gestational weeks 10-19 and identified at least 58 unique cell types/states contributing to the developing lung. We captured novel dynamic developmental trajectories from various progenitor cells that give rise to ciliated, pulmonary neuroendocrine cells, and other specialized cell types. We also identified four CFTR-expressing progenitor cell types and pinpointed the temporal emergence and spatial localization of these cell types. These developmental dynamics reveal broader epithelial cell plasticity and novel lineage hierarchies that were not previously reported. Combined with spatial transcriptomics, we identified both cell autonomous and non-cell autonomous signalling pathways that may dictate the temporal and spatial emergence of cell lineages. Finally, we showed that human pluripotent stem cell (hPSC)-derived fetal lung models capture similar cell lineage trajectories specifically through progenitor cells that express abundant levels of the CFTR gene. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from hPSC differentiations to similar developmental window.
