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. By applying a dual genetic lineage tracing approach, we specifically labeled TLPCs and found that they are bipotent, as they either differentiate into hepatocytes or re-adopt BEC fate. Mechanistically, Notch and Wnt/β-catenin signaling orchestrate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively. Together, our study provides functional and mechanistic insights into transdifferentiation-assisted liver regeneration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101857 | PMC |
| http://dx.doi.org/10.1038/s41588-023-01335-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Abnormal Venous Flow in Pregnant Women with Mild Right Ventricular Dysfunction in Repaired Tetralogy of Fallot: A Clinical Model for Organ Dysfunction in Preeclampsia.
J Clin Med
December 2024
Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Pregnant women with congenital heart disease carry a high risk of complications, especially when cardiac function is suboptimal. Increasing evidence suggests that impaired right ventricular (RV) function has a negative effect on placental function, possibly through venous congestion. We report a case series of hepatic and renal venous flow patterns in pregnant women with right ventricular dysfunction after repaired Tetralogy of Fallot (ToF), relative to those observed in normal pregnancy and preeclampsia.
View Article and Find Full Text PDFDNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.
Cancers (Basel)
December 2024
Division of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC) are the most common liver malignancies in children and young adults. FLC oncogenesis is associated with the generation of the fusion kinase, DNAJB1-PKAc (J-PKAc). J-PKAc has been found in 90% of FLC patients' tumors but not in other liver cancers.
View Article and Find Full Text PDFIntegrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis.
Int J Mol Sci
December 2024
Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mammalian blood cells originate from specialized 'hemogenic' endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs.
View Article and Find Full Text PDFinfection accelerates postnatal maturation of the intestinal epithelium.
Proc Natl Acad Sci U S A
January 2025
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen 52074, Germany.
Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.
View Article and Find Full Text PDFLate Ultra-High-Risk Recurrence of Gestational Trophoblastic Neoplasia Seven Years Posttreatment.
Cureus
December 2024
Obstetrics and Gynecology, University of Medicine and Pharmacy at Ho Chi Minh, Ho Chi Minh, VNM.
Gestational trophoblastic neoplasia (GTN) comprises a category of malignant or potentially malignant tumors that arise from gestational trophoblasts. Almost all cases of GTN experience a recurrence within the first year following treatment, although recurrences become rare after five years. Recurrent GTN tends to have a poor prognosis, primarily due to challenges in management, a high rate of relapse, and a low five-year survival rate.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!