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Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study
Author(s) -
Carpino Guido,
Renzi Anastasia,
Cardinale Vincenzo,
Franchitto Antonio,
Onori Paolo,
Overi Diletta,
Rossi Massimo,
Berloco Pasquale Bartolomeo,
Alvaro Domenico,
Reid Lola M.,
Gaudio Eugenio
Publication year - 2016
Publication title -
journal of anatomy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 118
eISSN - 1469-7580
pISSN - 0021-8782
DOI - 10.1111/joa.12418
Subject(s) - pdx1 , progenitor cell , biology , pancreatic duct , sox9 , pancreas , microbiology and biotechnology , progenitor , pathology , stem cell , medicine , endocrinology , insulin , islet , gene expression , gene , biochemistry
Pancreatic duct glands ( PDG s) are tubule‐alveolar glands associated with the pancreatic duct system and can be considered the anatomical counterpart of peribiliary glands ( PBG s) found within the biliary tree. Recently, we demonstrated that endodermal precursor niches exist fetally and postnatally and are composed functionally of stem cells and progenitors within PBG s and of committed progenitors within PDG s. Here we have characterized more extensively the anatomy of human PDG s as novel niches containing cells with multiple phenotypes of committed progenitors. Human pancreata ( n = 15) were obtained from cadaveric adult donors. Specimens were processed for histology, immunohistochemistry and immunofluorescence. PDG s were found in the walls of larger pancreatic ducts (diameters > 300 μm) and constituted nearly 4% of the duct wall area. All of the cells identified were negative for nuclear expression of Oct4, a pluripotency gene, and so are presumably committed progenitors and not stem cells. In the main pancreatic duct and in large interlobular ducts, Sox9 + cells represented 5–30% of the cells within PDG s and were located primarily at the bottom of PDG s, whereas rare and scattered Sox9 + cells were present within the surface epithelium. The expression of PCNA , a marker of cell proliferation, paralleled the distribution of Sox9 expression. Sox9 + PDG cells proved to be Pdx1 + /Ngn3 +/– /Oct4A − . Nearly 10% of PDG cells were positive for insulin or glucagon. Intercalated ducts contained Sox9 + /Pdx1 + /Ngn3 + cells, a phenotype that is presumptive of committed endocrine progenitors. Some intercalated ducts appeared in continuity with clusters of insulin‐positive cells organized in small pancreatic islet‐like structures. In summary, PDG s represent niches of a population of Sox9 + cells exhibiting a pattern of phenotypic traits implicating a radial axis of maturation from the bottoms of the PDG s to the surface of pancreatic ducts. Our results complete the anatomical background that links biliary and pancreatic tracts and could have important implications for the common patho‐physiology of biliary tract and pancreas.