Lgr5
| Autor: | Nicole, Prior, Christopher J, Hindley, Fabian, Rost, Elena, Meléndez, Winnie W Y, Lau, Berthold, Göttgens, Steffen, Rulands, Benjamin D, Simons, Meritxell, Huch |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Organoid Cell Culture Techniques Embryonic Development Cell Count Receptors G-Protein-Coupled Mice Lgr5 Animals Homeostasis Cell Lineage Alleles Cells Cultured Microscopy Confocal Base Sequence Liver development Stem Cells Gene Expression Regulation Developmental Cell Differentiation Epithelial Cells Stem Cells and Regeneration Liver Hepatocytes Bipotent Female Liver stem/progenitor cells Hepatoblast |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 |
| Popis: | During mouse embryogenesis, progenitors within the liver known as hepatoblasts give rise to adult hepatocytes and cholangiocytes. Hepatoblasts, which are specified at E8.5-E9.0, have been regarded as a homogeneous progenitor population that initiate differentiation from E13.5. Recently, scRNA-seq analysis has identified sub-populations of transcriptionally distinct hepatoblasts at E11.5. Here, we show that hepatoblasts are not only transcriptionally but also functionally heterogeneous, and that a subpopulation of E9.5-E10.0 hepatoblasts exhibit a previously unidentified early commitment to cholangiocyte fate. Importantly, we also identify a subpopulation constituting 2% of E9.5-E10.0 hepatoblasts that express the adult stem cell marker Lgr5, and generate both hepatocyte and cholangiocyte progeny that persist for the lifespan of the mouse. Combining lineage tracing and scRNA-seq, we show that Lgr5 marks E9.5-E10.0 bipotent liver progenitors residing at the apex of a hepatoblast hierarchy. Furthermore, isolated Lgr5+ hepatoblasts can be clonally expanded in vitro into embryonic liver organoids, which can commit to either hepatocyte or cholangiocyte fates. Our study demonstrates functional heterogeneity within E9.5 hepatoblasts and identifies Lgr5 as a marker for a subpopulation of bipotent liver progenitors. Summary: Multicolour clonal genetic lineage tracing, organoid cultures and scRNA-seq analyses demonstrate that Lgr5 marks a subpopulation of bipotent hepatoblasts that reside at the apex of the hierarchy of a heterogenous hepatoblast pool. |
| Databáze: | OpenAIRE |
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