Single-Cell Transcriptomic Profiling of Cholangiocyte Organoids Derived from Bile Ducts of Primary Sclerosing Cholangitis Patients.

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.

Functional ProTracer identifies patterns of cell proliferation in tissues and underlying regulatory mechanisms.

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.

Distinct hepatocyte identities in liver homeostasis and regeneration.

The process of metabolic liver zonation is spontaneously established by assigning distributed tasks to hepatocytes along the porto-central blood flow. Hepatocytes fulfil critical metabolic functions, while also maintaining hepatocyte mass by replication when needed. Recent technological advances have enabled us to fine-tune our understanding of hepatocyte identity during homeostasis and regeneration.

Hepatic stellate cells: From bad reputation to mediators of liver homeostasis.

Organ size and function critically depend on the tight regulation of cellular turnover. In this issue of Trinh . reveal that hepatic stellate cells play an important role in maintaining liver homeostasis by stimulating midzonal hepatocyte proliferation through the secretion of neurotrophin-3.

Bipotent transitional liver progenitor cells contribute to liver regeneration.

Following severe liver injury, when hepatocyte-mediated regeneration is impaired, biliary epithelial cells (BECs) can transdifferentiate into functional hepatocytes. However, the subset of BECs with such facultative tissue stem cell potential, as well as the mechanisms enabling transdifferentiation, remains elusive. Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe liver injury.

Spatiotemporal Metabolic Liver Zonation and Consequences on Pathophysiology.

Hepatocytes are the main workers in the hepatic factory, managing metabolism of nutrients and xenobiotics, production and recycling of proteins, and glucose and lipid homeostasis. Division of labor between hepatocytes is critical to coordinate complex complementary or opposing multistep processes, similar to distributed tasks at an assembly line. This so-called metabolic zonation has both spatial and temporal components.

Effects of CBCT acquisition protocol and additional superimposed computerized optical impressions on the accuracy of root canal length measurements: an ex vivo study.

Aim: The purpose of the present investigation was to evaluate the accuracy of root canal length (RCL) determination according to CBCT acquisition protocol and evaluate the influence of additional superimposed computerized optical impressions.

Materials And Methods: CBCT scans with low-dose (LD) and high-definition (HD) protocols as well as computerized optical impressions of 30 extracted human molars were acquired. Sicat Endo software (Sicat) was used for CBCT RCL measurements with (LD+, HD+) and without (LD-, HD-) a superimposed optical impression.

Loss of Hepatic Leucine-Rich Repeat-Containing G-Protein Coupled Receptors 4 and 5 Promotes Nonalcoholic Fatty Liver Disease.

The roof plate-specific spondin-leucine-rich repeat-containing G-protein coupled receptor 4/5 (LGR4/5)-zinc and ring finger 3 (ZNRF3)/ring finger protein 43 (RNF43) module is a master regulator of hepatic Wnt/β-catenin signaling and metabolic zonation. However, its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. The current study investigated whether hepatic epithelial cell-specific loss of the Wnt/β-catenin modulator Lgr4/5 promoted NAFLD.

Multicellular dynamics of zonal liver regeneration mapped in space and time.

In this issue, Ben-Moshe et al. (2022) use spatiotemporally resolved single-cell and spatial transcriptomic profiling to dissect the multicellular dynamics enabling zonal liver regeneration. They highlight how pan-zonal compensatory hepatocyte proliferation, transient reprogramming of peri-injury hepatocytes, and concerted zonated action of different liver cell types orchestrate the healing process.

Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites.

The Hippo/YAP pathway controls cell proliferation through sensing physical and spatial organization of cells. How cell-cell contact is sensed by Hippo signaling is poorly understood. Here, we identified the cell adhesion molecule KIRREL1 as an upstream positive regulator of the mammalian Hippo pathway.

The RSPO-LGR4/5-ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease.

WNT/β-catenin signaling plays pivotal roles during liver development, homeostasis, and regeneration. Likewise, its deregulation disturbs metabolic liver zonation and is responsible for the development of a large number of hepatic tumors. Liver fibrosis, which has become a major health burden for society and a hallmark of NASH, can also be promoted by WNT/β-catenin signaling.

Genome-wide screening in human kidney organoids identifies developmental and disease-related aspects of nephrogenesis.

Human organoids allow the study of proliferation, lineage specification, and 3D tissue development. Here we present a genome-wide CRISPR screen in induced pluripotent stem cell (iPSC)-derived kidney organoids. The combination of inducible genome editing, longitudinal sampling, and endpoint sorting of tubular and stromal cells generated a complex, high-quality dataset uncovering a broad spectrum of insightful biology from early development to "adult" epithelial morphogenesis.

ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation.

AXIN2 and LGR5 mark intestinal stem cells (ISCs) that require WNT/β-Catenin signaling for constant homeostatic proliferation. In contrast, AXIN2/LGR5+ pericentral hepatocytes show low proliferation rates despite a WNT/β-Catenin activity gradient required for metabolic liver zonation. The mechanisms restricting proliferation in AXIN2+ hepatocytes and metabolic gene expression in AXIN2+ ISCs remained elusive.

Design and verification of a measurement setup for wireless remote microphone systems (WRMSs).

Objective: This work presents the design and verification of a simplified measurement setup for wireless remote microphone systems (WRMSs), which has been incorporated into guidelines of the European Union of Hearing Aid Acousticians (EUHA).

Design: Three studies were conducted. First, speech intelligibility scores within the simplified setup were compared to that in an actual classroom.

Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair.

Organ homeostasis is orchestrated by time- and spatially restricted cell proliferation. Studies identifying cells with superior proliferative capacities often rely on the lineage tracing of a subset of cell populations, which introduces a potential selective bias. In this work, we developed a genetic system [proliferation tracer (ProTracer)] by incorporating dual recombinases to seamlessly record the proliferation events of entire cell populations over time in multiple organs.

The Conundrum of the Pericentral Hepatic Niche: WNT/-Catenin Signaling, Metabolic Zonation, and Many Open Questions.

WNT/-catenin signaling promotes stemness, proliferation, and cell fate decisions in various tissue stem cell compartments, which maintain organs with a high turnover of cells (e.g., skin, stomach, and gut).

Clinical management of fusion in primary mandibular incisors: a systematic literature review.

Dental anomalies occurring in deciduous teeth can affect the eruption of the permanent dentition and the occlusion stability. The occurrence of dental anomalies such as double teeth during the primary dentition in the daily practice might be frequent. The study aimed to qualitatively summarize the therapeutic management of double teeth in primary incisors.

Computerized optical impression making of edentulous jaws - An in vivo feasibility study.

Purpose: Within the specialty of prosthodontics, oral impressions are ubiquitous tools utilized to transfer intraoral characteristics such as teeth, implants, and soft tissue into a physical state (stone cast) that is processable in a laboratory setting for the fabrication of dental restorations. In recent years, optical impression systems have become ubiquitous in clinical practice replacing the conventional method of impression making. The purpose of the present study was to evaluate the feasibility and accuracy of computerized optical impression making of edentulous jaws in an in vivo setting.