During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3(-/-) mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta cells from stem cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746519 | PMC |
| http://dx.doi.org/10.1016/j.ydbio.2011.08.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Toxic Effects of Cobalt on Erythroid Progenitor Cells.
Chem Res Toxicol
January 2025
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Cobalt is a crucial trace element that widely exists in natural environments and is necessary for normal physiological function. However, excessive cobalt exposure leads to various adverse health effects, especially hematological and endocrine dysfunctions. Here, we investigated the toxicity of cobalt on early erythropoiesis by using ex vivo cultured erythroid progenitor cells (EPCs).
View Article and Find Full Text PDFMechanistic insights into cardiac regeneration and protection through MEIS inhibition.
Turk J Biol
October 2024
Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, İstanbul, Turkiye.
Article Synopsis
- MEIS1 is a key regulator in stopping cardiomyocyte cell division and is a potential target for heart-related therapies.
- Inhibition of MEIS1 through new small molecules (MEISi-1 and MEISi-2) boosts the growth and division of neonatal cardiomyocytes significantly compared to untreated cells.
- MEIS1 inhibition not only reduces the expression of certain target genes but also enhances important cardiac-specific gene expression, suggesting these inhibitors could play a vital role in heart regeneration treatments.
Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis.
EBioMedicine
January 2025
Department of Respiratory and Clinical Care Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. Electronic address:
Background: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with restrictive ventilation. Recently, the structural and functional defects of small airways have received attention in the early pathogenesis of IPF. This study aimed to elucidate the characteristics of small airway epithelial dysfunction in patients with IPF and explore novel therapeutic interventions to impede IPF progression by targeting the dysfunctional small airways.
View Article and Find Full Text PDFCharacterisation and hierarchy of the spermatogonial stem cell compartment in human spermatogenesis by spectral cytometry using a 16-colors panel.
Cell Mol Life Sci
December 2024
Université Paris-Saclay, CEA, UMR Stabilité Génétique Cellules Souches Et Radiations, iRCM/IBFJ, Laboratoire Des Cellules Souches Germinales, 92265, Fontenay-Aux-Roses, France.
About one in six couples experience fertility problems, and male infertility accounts for about half of these cases. Spermatogenesis originates from a small pool of spermatogonial stem cells (SSCs), which are of interest for the treatment of infertility but remain poorly characterised in humans. Using multiparametric spectral flow cytometric analysis with a 16-colours (16-C) panel of cell markers, we identify novel markers of SSCs and provide insights into unravelling and resolving the heterogeneity of the human spermatogonial cells.
View Article and Find Full Text PDFSDF-1/CXCR4 axis maintains porcine prospermatogonia undifferentiated state through regulation of transcription suppressor PLZF.
Theriogenology
March 2025
Germline Stem Cells and Microenvironment Lab, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China; Stem Cell Research and Translation Center, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:
Prospermatogonia (ProSGs), the progenitors of spermatogonial stem cells in neonatal testes, undergo critical migration to the testicular microenvironment-a fundamental process for testicular development and subsequent spermatogenic capacity. The SDF-1/CXCR4 chemokine axis serves as an essential molecular guidance mechanism, directing ProSGs toward the basal membrane of seminiferous tubules. Nevertheless, the precise molecular mechanisms governing this axis remain incompletely understood.
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!