Chronic liver injury can cause cirrhosis and impaired liver regeneration, impairing organ function. Adult livers can regenerate in response to parenchymal insults, and multiple cellular sources have been reported to contribute to this response. In this study, we modeled human chronic liver injuries, in which such responses are blunted, without genetic manipulations, and assessed potential contributions of non-parenchymal cells (NPCs) to hepatocyte regeneration. We show that NPC-derived hepatocytes replenish a large fraction of the liver parenchyma following severe injuries induced by long-term thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment. Through lineage tracing of biliary epithelial cells (BECs), we show that BECs are a source of new hepatocytes and gain an Hnf4αCK19 bi-phenotypic state in periportal regions and fibrotic septa. Bi-phenotypic cells were also detected in cirrhotic human livers. Together, these data provide further support for hepatocyte regeneration from BECs without genetic interventions and show their cellular plasticity during severe liver injury.
The liver, whose major functional cell type is the hepatocyte, is a peculiar organ with remarkable regenerative capacity. The widely held notion that hepatic progenitor cells contribute to injury-induced liver regeneration has long been debated. However, multiple lines of evidence suggest that the plasticity of differentiated cells is a major mechanism for the cell source in injury-induced liver regeneration. Investigating cell plasticity could potentially expand our understanding of liver physiology and facilitate the development of new therapies for liver diseases. In this review, we summarize the cell sources for hepatocyte regeneration and the clinical relevance of cell plasticity for human liver diseases. We focus on mechanistic insights on the injury-induced cell plasticity of hepatocytes and biliary epithelial cells and discuss future directions for investigation. Specifically, we propose the notion of 'reprogramming competence' to explain the plasticity of differentiated hepatocytes. Liver Regeneration and Cell PlasticityThe liver harbors remarkable regenerative capacity and performs multiple physiological functions [1,2]. However, as this organ is central for metabolism and detoxification, it often suffers extraneous injury and gradually loses its regenerative ability [1,2]. Understanding the mechanisms of liver regeneration is a fundamental topic in liver biology. Since hepatocytes are the primary effector cells for liver physiological functions, the cell source for new hepatocytes after injury has been a main focus in liver regeneration research. It has long been debated whether stem cells contribute to injury-induced liver regeneration. However, recent studies have shown that cell sources other than stem cells also contribute to injury-induced liver regeneration [3]. Cell reprogrammingthat is, the plasticity of hepatocytes and biliary epithelial cellshas been identified as a major pathway to generate new hepatocytes in response to liver injury. Therefore, a better understanding of the underlying mechanisms of injury-induced cell plasticity in vivo may facilitate the development of cell-plasticitybased therapies. In this review, we summarize the latest findings on cell sources with mechanistic regulation in liver regeneration and discuss their clinical relevance to human liver diseases. Liver Homeostasis under Physiological ConditionsIt has long been proposed that the liver harbors liver progenitor cells (LPCs) in the canal of Hering, a structure that connects bile canaliculi with bile ducts in periportal areas, to fulfil liver regeneration requirements under normal physiological conditions [2]. LPCs are characterized based on the following properties: (i) clonogenic ability with high proliferation potential; (ii) the ability to differentiate into both hepatocytes and cholangiocytes under culture conditions; and (iii) liver repopulation ability after transplantation [2]. The 'streaming liver' model was proposed decades ago to describe the contribution of LPCs to in vivo liver homeostasis. This model de...
Context. In Gaia DR2, an unprecedented high level of precision has been reached at sub-milliarcsecond for astrometry and millimagnitudes for photometry. Using cluster members identified with the astrometry and photometry in Gaia DR2, we can obtain a reliable determination of cluster properties. However, because of the shortcomings of Gaia spectroscopic observations in dealing with densely crowded cluster regions, the RVs and metallicity values for cluster member stars from Gaia DR2 are still lacking. It is necessary to combine the Gaia data with the data from large spectroscopic surveys, such as LAMOST, APOGEE, GALAH, and Gaia-ESO. Aims. In this study our aim is to improve the cluster properties by combining the LAMOST spectra. In particular, we provide the list of cluster members with spectroscopic parameters as an add-value catalog in LAMOST DR5, which can be used to perform a detailed study for a better understanding of the stellar properties, by using their spectra and fundamental properties from the host cluster. Methods. We cross-matched the spectroscopic catalog in LAMOST DR5 with the identified cluster members in Cantat-Gaudin et al. (2018, A&A, 618, A93). We then used members with spectroscopic parameters to derive statistical properties of open clusters. Results. We obtained a list of 8811 members with spectroscopic parameters and a catalog of 295 cluster properties. The provided cluster properties include astrometric parameters, spectroscopic parameters, derived kinematic and orbital parameters, and isochrone fitting results. In addition, we study the radial and vertical metallicity gradient and age-metallicity relation with the compiled open clusters as tracers, finding slopes of −0.053 ± 0.004 dex kpc−1, −0.252 ± 0.039 dex kpc−1, and 0.022 ± 0.008 dex Gyr−1, respectively. The slopes of the metallicity distribution relation for young clusters (0.1 Gyr < Age < 2 Gyr) and the age-metallicity relation for clusters within 6 Gyr are both consistent with the literature results. In order to fully study the chemical evolution history in the disk, more spectroscopic observations for old and distant open clusters are needed for further investigation.
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