Human fetal lung tip progenitor cells
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PROVIDER: PRJNA784950 | ENA |
REPOSITORIES: ENA
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Project description:In order to understand transcription factor SOX2 and SOX9 function, we have knocked down SOX2 and SOX9 in human fetal lung tip progenitor organoids using an inducible CRISPRi system. We discovered that SOX2 knockdown didn't appear to influence organoid cell survival and led to minimal gene expression changes at transcriptome level. By contrast, SOX9 knockdown led to organoid cell self-renewal defects and we have detected hundreds of genes differentially expressed after SOX9 knockdown.
2022-04-30 | GSE189884 | GEO
Project description:Underdeveloped lungs are a primary cause of morbidity and mortality in premature infants, but our ability to help these patients by speeding up lung development are hindered by a lack of understanding of human lung developmental biology. Here, we performed single cell RNA sequencing of the human fetal lung from samples spanning from 11.5 weeks gestation to 21 weeks gestation from the distal lung, middle airways, and the tracheal epithelium. The primary goal of this experiment was to define fetal cell states to serve as a gold standard for pluripotent stem cell-derived lung cells and tissues, and to identify potential signaling pathways that drive differentiation of lung progenitor cells to mature cell types. Additionally, we generated bud tip progenitor organoids from 12 week human fetal lung bud tip progenitors. We show that treatment of bud tip progenitor organoids with a short pulse of dual SMAD activation (BMP4+TGFb1) led to the upregulation of lung basal cell markers, a cell type that serves as a critical stem cell for the adult airway, and that further treatment with dual SMAD inhibition leads to the generation of airway-like organoids containing differentiated cell types of the adult airway, including basal stem cells.
2020-04-17 | E-MTAB-8221 | biostudies-arrayexpress
Project description:Epithelial tip progenitor cells are an important epithelial progenitor population in the developing lung. At early stages of development they produce SOX2+ bronchiolar progenitor cells. At later stages of embryonic lung development they produce SOX2- alveolar progenitor cells. We purified the tip progenitor cells from early (E11.5, bronchiolar progenitor producing) and late (E17.5, alveolar progenitor producing) stages of mouse lung development and used Affymetrix microarrays to compare their gene expression profiles.
2016-08-31 | GSE75860 | GEO
Project description:RNASeq to investigate SOX2 and SOX9 function in human fetal lung tip progenitor cells
| PRJNA784953 | ENA
Project description:Underdeveloped lungs are the primary cause of death in premature infants, however, little is known about stem and progenitor cell maintenance during human lung development. In this study, we have identified that FGF7, Retinoic Acid and CHIR-99021, a small molecule that inhibits GSK3 to activate Wnt signaling, support in vitro maintenance of primary human fetal lung bud tip progenitor cells in a progenitor state. Furthermore, these factors are sufficient to derive a population of human bud tip-like progenitor cells in 3D organoid structures from human pluripotent stem cells (hPSC). Functional studies showed that hPSC-derived bud tip progenitor organoids do not contain any mesenchymal cell types, maintain multilineage potential in vitro and are able to engraft into the airways of injured mice and respond to systemic factors. We performed RNA-sequencing to assess the degree of similarity in global gene expression profiles between the full human fetal lung (59-127 days gestation), isolated human fetal bud tip progenitors, organoids grown from primary fetal bud tip progenitors, and hPSC-derived bud tip organoids. Results showed that hPSC-derived organoids have molecular profiles similar to organoids generated from primary human fetal lung tissue. Gene expression differences between hPSC-derived bud tip organoids and fetal progenitor organoids may be related to the presence of contaminating mesenchymal cells in primary cultures. hPSC-derived bud tip organoids are generated from a well-defined human cell sources, offering a distinct advantage over rare primary tissue as a means to study human specific lung development, homeostasis and disease.<br>Sample Nomenclature - Description<br> -------------------------------------------------------------------------<br> Peripheral fetal lung the distal/peripheral portion of the fetal lung (i.e., distal 0.5 cm) was excised from the rest of the lung using a scalpel. This includes all components of the lung (e.g., epithelial, mesenchymal, vascular). <br>Isolated fetal bud tip the bud peripheral portion of the fetal lung was excised with a scalpel and subjected to enzymatic digestion and microdissection. The epithelium was dissected and separated from the mesenchyme, but a small amount of associated mesenchyme likely remained. <br>Fetal progenitor organoid 3D organoid structures that arose from culturing isolated fetal epithelial bud tips. <br>Foregut spheroid 3D foregut endoderm structure as described in Dye et al. (2015). Gives rise to patterned lung organoid (PLO) when grown in 3F medium. <br> Patterned lung organoid (PLO) lung organoids that were generated by differentiating hPSCs, as described throughout the manuscript. <br> Bud tip organoid organoids derived from PLOs, enriched for SOX2/SOX9 co-expressing cells, and grown/passaged in 3F medium.
2018-11-17 | E-MTAB-6023 | biostudies-arrayexpress
Project description:Human fetal lung tip cells were purifed from developing human lungs at pseudoglandular and canalicular stages and in vitro cultured as organoids. Whole transcriptomic data for each organoid line at different stages were profiled by RNA seq.
2022-09-30 | GSE178528 | GEO
Project description:In order to understand transcription factor ETV4 and ETV5 function, we have knocked down ETV4 and ETV5 synergistically in human foetal lung tip progenitor organoids using an inducible CRISPRi system. We discovered that ETV double knockdown led to organoid cell self-renewal defects
2022-07-02 | GSE207179 | GEO
Project description:Human fetal lung tip cells were purifed from developing human lungs at pseudoglandular and canalicular stages and in vitro cultured as organoids. Chromatin accessibility data for each organoid line at different stages were profiled by ATAC-seq.
2022-09-30 | GSE178527 | GEO
Project description:Human fetal lung tip cells were purifed from developing human lungs at pseudoglandular in vitro cultured as organoids. Whole transcriptomic data for 3 organoid lines received different signalling inhibitors were profiled by RNA seq.
2022-09-30 | GSE211308 | GEO
Project description:Significant progress has been made in recent years in characterizing human multipotent progenitor cells (hMPCs) of the early pancreas; however, the identity and persistence of these cells during the second trimester, after the initiation of branching morphogenesis, remain elusive. Additionally, studies on hMPCs have been hindered by few isolation methods that allow for the recovery of live cells. Here, we investigated the tip progenitor domain in the branched epithelium of human fetal pancreas between 13.5 and 17.5 gestational weeks by immunohistological staining. We also used a novel RNA‐based technology to isolate live cells followed by gene expression analyses. We identified cells co‐expressing SOX9 and PTF1A, two transcription factors known to be important for pancreatic MPCs, within the tips of the epithelium and observed a decrease in their proportions over time. Pancreatic SOX9+/PTF1A+ cells were enriched for MPC markers, including MYC and GATA6. These cells were proliferative and appeared active in branching morphogenesis and matrix remodeling, as evidenced by gene set enrichment analysis. We identified a hub of genes pertaining to the expanding tip progenitor niche, such as FOXF1, GLI3, TBX3, FGFR1, TGFBR2, ITGAV, ITGA2, and ITGB3. YAP1 of the Hippo pathway emerged as a highly enriched component within the SOX9+/PTF1A+ cells. Single‐cell RNA‐sequencing further corroborated the findings by identifying a cluster of SOX9+/PTF1A+ cells with multipotent characteristics. Based on these results, we propose that the SOX9+/PTF1A+ cells in the human pancreas are uncommitted MPC‐like cells that reside at the tips of the expanding pancreatic epithelium, directing self‐renewal and inducing pancreatic organogenesis.
2019-11-27 | GSE141087 | GEO