Publications by authors named "J S Tchorz"
Article Synopsis
- This study investigates cellular senescence and its impact on aging and disease, focusing on the roles of different cell types, particularly in the context of liver injury and repair.
- Researchers created a set of genetic tools to trace and manipulate p16 cell types in vivo, revealing that macrophages and endothelial cells (ECs) have unique roles and outcomes in liver fibrosis and regeneration.
- Findings show that removing senescent macrophages helps reduce liver damage, while clearing senescent ECs worsens it; additionally, enhancing EC function through a specific gene reduces fibrosis, suggesting potential strategies for targeted therapies.
Background And Aims: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disorder without effective medical treatment which is characterized by inflammation and fibrotic structures around the bile ducts. Biliary epithelial cells (cholangiocytes) are the target and potential disease drivers in PSC, yet little is known if cholangiocytes from PSC patients differ from non-PSC controls. To characterize cholangiocytes at early rather than end-stage disease, cholangiocyte organoids (COs) were derived from diseased bile ducts of PSC patients and compared to organoids generated from disease controls.
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- The YAP/Hippo pathway regulates organ growth and helps maintain stem cell function, with LATS kinases playing a critical role by inactivating YAP.
- A new small-molecule inhibitor, NIBR-LTSi, has been developed that selectively targets LATS kinases, activating YAP signaling and promoting tissue regeneration in laboratory settings.
- While NIBR-LTSi shows promise by enhancing liver regeneration and supporting stem cell characteristics, prolonged use may lead to excessive cell proliferation and dedifferentiation, which could limit its therapeutic benefits.
A genetic system, ProTracer, has been recently developed to record cell proliferation in vivo. However, the ProTracer is initiated by an infrequently used recombinase Dre, which limits its broad application for functional studies employing floxed gene alleles. Here we generated Cre-activated functional ProTracer (fProTracer) mice, which enable simultaneous recording of cell proliferation and tissue-specific gene deletion, facilitating broad functional analysis of cell proliferation by any Cre driver.
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