ArticleStem cells translational medicine2019
SOX9+/PTF1A+ Cells Define the Tip Progenitor Cells of the Human Fetal Pancreas of the Second Trimester.
Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Mapping histologic and functional maturation of human endocrine pancreas across early postnatal periods.Nature communications · 2026Article
- SOX9: dosage- and context-dependent functions in pancreatic development and β-cell biology.Cell communication and signaling : CCS · 2026Review
- The Hippo signaling pathway modulates pancreatic tissue homeostasis.Cell death discovery · 2025Review
- Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma.Hepatobiliary surgery and nutrition · 2024Article
- Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury.Stem cells (Dayton, Ohio) · 2024Article
- An Insight into Vital Genes Responsible for β-cell Formation.Advances in experimental medicine and biology · 2024Article
- Integrin α2 in the microenvironment and the tumor compartment of digestive (gastrointestinal) cancers: emerging regulators and therapeutic opportunities.Frontiers in oncology · 2024Review
- Identification and Characterization of the Wilms Tumor Cancer Stem Cell.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Ptf1a function and transcriptional cis-regulation, a cornerstone in vertebrate pancreas development.The FEBS journal · 2022Review
- SmartFlareWorld journal of stem cells · 2021Article
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- A Transcriptionally Distinct Subpopulation of Healthy Acinar Cells Exhibit Features of Pancreatic Progenitors and PDAC.Cancer research · 2021Article
- Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip.Nature biomedical engineering · 2021Article
- Temporal single-cell regeneration studies: the greatest thing since sliced pancreas?Trends in endocrinology and metabolism: TEM · 2021Review
- A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion.Nature communications · 2021Article
- Discoveries in Pancreatic Physiology and Disease Biology Using Single-Cell RNA Sequencing.Frontiers in cell and developmental biology · 2021Review
- Monogenic Diabetes Modeling:Frontiers in endocrinology · 2021Review
- Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer.Clinical epigenetics · 2020Article
- Identifying Drug Targets in Pancreatic Ductal Adenocarcinoma Through Machine Learning, Analyzing Biomolecular Networks, and Structural Modeling.Frontiers in pharmacology · 2020Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Significant progress has been made in recent years in characterizing human multipotent progenitor cells (hMPCs) of the early pancreas; however, the identity and persistence of these cells during the second trimester, after the initiation of branching morphogenesis, remain elusive. Additionally, studies on hMPCs have been hindered by few isolation methods that allow for the recovery of live cells. Here, we investigated the tip progenitor domain in the branched epithelium of human fetal pancreas between 13.5 and 17.5 gestational weeks by immunohistological staining. We also used a novel RNA-based technology to isolate live cells followed by gene expression analyses. We identified cells co-expressing SOX9 and PTF1A, two transcription factors known to be important for pancreatic MPCs, within the tips of the epithelium and observed a decrease in their proportions over time. Pancreatic SOX9+/PTF1A+ cells were enriched for MPC markers, including MYC and GATA6. These cells were proliferative and appeared active in branching morphogenesis and matrix remodeling, as evidenced by gene set enrichment analysis. We identified a hub of genes pertaining to the expanding tip progenitor niche, such as FOXF1, GLI3, TBX3, FGFR1, TGFBR2, ITGAV, ITGA2, and ITGB3. YAP1 of the Hippo pathway emerged as a highly enriched component within the SOX9+/PTF1A+ cells. Single-cell RNA-sequencing further corroborated the findings by identifying a cluster of SOX9+/PTF1A+ cells with multipotent characteristics. Based on these results, we propose that the SOX9+/PTF1A+ cells in the human pancreas are uncommitted MPC-like cells that reside at the tips of the expanding pancreatic epithelium, directing self-renewal and inducing pancreatic organogenesis. Stem Cells Translational Medicine 2019;8:1249&1264.
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