lnc‐RHL, a novel long non‐coding RNA required for the differentiation of hepatocytes from human bipotent progenitor cells
| Autor: | Wu He, Adara Bochanis, José E. Manautou, Soowan Lee, Theodore P. Rasmussen, Bindu Prabhakar |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Regulator Biology Cholangiocyte Young Adult lnc‐RHL 03 medical and health sciences lncRNA 0302 clinical medicine Downregulation and upregulation In vivo hepatocyte medicine Humans Cell Lineage RNA Small Interfering Progenitor cell Child hepatic progenitor cells Gene knockdown Chromosomes Human Pair 11 Stem Cells Cell Differentiation Hep G2 Cells Original Articles differentiation Cell Biology General Medicine Long non-coding RNA Cell biology Apolipoproteins 030104 developmental biology medicine.anatomical_structure Hepatocyte Nuclear Factor 4 Liver Doxorubicin Multigene Family 030220 oncology & carcinogenesis Hepatocyte HepaRG cells Hepatocytes Female RNA Interference RNA Long Noncoding Original Article cholangiocyte |
| Zdroj: | Cell Proliferation |
| ISSN: | 1365-2184 0960-7722 |
| DOI: | 10.1111/cpr.12978 |
| Popis: | Objectives The final stage of liver development is the production of hepatocytes and cholangiocytes (biliary epithelial cells) from bipotent hepatic progenitor cells. We used HepaRG cells, which are bipotent and able to differentiate into both hepatocytes and cholangiocytes, as a model to study the action of a novel lncRNA (lnc‐RHL) and its role in the regulation of bipotency leading to hepatocytes and cholangiocytes. Materials and Methods Differentiation of HepaRG cells was assessed by marker expression and morphology which revealed their ability to differentiate into hepatocytes and cholangiocytes (modelling the behaviour of hepatoblasts in vivo). Using a qRT‐PCR and RACE, we cloned a novel lncRNA (lnc‐RHL; regulator of hepatic lineages) that is upregulated upon HepaRG differentiation. Using inducible knockdown of lnc‐RHL concurrently with differentiation, we show that lnc‐RHL is required for proper HepaRG cell differentiation resulting in diminution of the hepatocyte lineage. Results Here, we report the discovery of lnc‐RHL, a spliced and polyadenylated 670 base lncRNA expressed from the 11q23.3 apolipoprotein gene cluster. lnc‐RHL expression is confined to hepatic lineages and is upregulated when bipotent HepaRG cells are caused to differentiate. HepaRG cells made deficient for lnc‐RHL have reduced ability to differentiate into hepatocytes, but retain their ability to differentiate into cholangiocytes. Conclusions Deficiency for lnc‐RHL in HepaRG cells converts them from bipotent progenitor cells to unipotent progenitor cells with impaired ability to yield hepatocytes. We conclude that lnc‐RHL is a key regulator of bipotency in HepaRG cells. HepaRG cells serve as a useful model of hepatic differentiation. A novel lncRNA (lnc‐RHL) is induced when bipotent hepatic progenitor cells are induced to differentiate. Using inducible knockdown approaches, we show that lnc‐RHL regulates the final stage of liver development in which hepatocytes and cholangiocytes are formed from bipotent progenitor cells. Deficiency for lnc‐RHL alters the balance of hepatocytes and cholangiocytes over the course of differentiation. |
| Databáze: | OpenAIRE |
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