Lung tumorigenic model employing human pluripotent stem cell-derived lung organoids that conditionally overexpress HER2
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE163557 | GEO | 2020/12/21
REPOSITORIES: GEO
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Project description:Lung tumorigenic model employing human pluripotent stem cell-derived lung organoids that conditionally overexpress HER2
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Project description:Mesenchymal Stem/Stromal Cells (MSC) obtained from Pluripotent Stem Cells (PSC) constitute an interesting alternative to classical MSC in regenerative medicine. Amongst one of their many mechanism of action, MSC extracellular vesicles (EVs) raise as a suitable substitution of MSC in future cell-free based therapeutics approaches. EVs, unlike cells, do not elicit acute immune rejection and can be produced in large quantities and stored ready to use, until needed. Though therapeutic potential of MSC-EVs had already been proved, thorough characterization of them is still scarce. In this work we performed a label-free Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) proteomic approach to identify the most abundant proteins in EVs secreted from MSC derived from PSC (PD-MSC) and from their parental iPSC. Next, we compared both datasets finding that while iPSC EVs enclose proteins that modulates RNA and miRNA stability and protein sorting, PD-MSC EVs are rich in proteins that organize extracellular matrix, regulate locomotion and influence cell-substrate adhesion. Moreover, when compared to their respective cells, iPSC and iPSC EVs share a greater proportion of proteins while PD-MSC proteome seems to be more specific. Correlation and Principal Component Analysis consistently aggregate iPSC and iPSC EVs but segregate PD-MSC and their EVs. Altogether these findings suggest that during differentiation, PD-MSC EVs acquire a more specific set of proteins than their parental iPSC�s EVs have and that, arguably, this might confer them their therapeutic properties.
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Project description:The lung epithelium is derived from the endodermal germ layer, which undergoes a complex series of endoderm-mesoderm-mediated signaling events to generate the final arborized network of conducting airways (bronchi, bronchioles) and gas-exchanging units (alveoli). These stages include endoderm induction, anterior-posterior and dorsal-ventral patterning, lung specification, lung budding, branching morphogenesis, and, finally, maturation. Here we describe a protocol that recapitulates several of these milestones in order to differentiate human pluripotent stem cells (hPSCs) into ventral-anterior foregut spheroids and further into two distinct types of organoids: human lung organoids and bud tip progenitor organoids. The resulting human lung organoids possess cell types and structures that resemble the bronchi/bronchioles of the developing human airway surrounded by lung mesenchyme and cells expressing alveolar-cell markers. The bud tip progenitor organoids possess a population of highly proliferative multipotent cells with in vitro multilineage differentiation potential and in vivo engraftment potential. Human lung organoids can be generated from hPSCs in 50-85 d, and bud tip progenitor organoids can be generated in 22 d. The two hPSC-derived models presented here have been benchmarked with human fetal tissue and found to be representative of human fetal-like tissue. The bud tip progenitor organoids are thus ideal for exploring epithelial fate decisions, while the human lung organoids can be used to model epithelial-mesenchymal cross-talk during human lung development. In addition to their applications in developmental biology, human lung organoids and bud tip progenitor organoids may be implemented in regenerative medicine, tissue engineering, and pharmaceutical safety and efficacy testing.
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