Out of the F-box: Reawakening the Pancreas

Seifert, Bryce A.

doi:10.1016/j.stem.2014.07.006

Cited by 7 publications

(9 citation statements)

References 10 publications

(10 reference statements)

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“…This interpretation corroborates the findings of others that there are no stem cells, only committed progenitors, in the pancreas postnatally (Zhou et al. ; Seifert & Xiong, ).…”

Section: Introductionsupporting

confidence: 92%

“…) and others (Zhou et al. ; Seifert & Xiong, ). A restricted Sox9 + sub‐population also expressed Ngn3, indicating features associated with the endocrine specification (Gomez et al.…”

Section: Discussionmentioning

confidence: 89%

“…; Wang et al. ; Seifert & Xiong, ). Therefore, nuclear, not cytoplasmic, expression of Oct4A was evaluated to identify true stem cells.…”

Section: Methodsmentioning

confidence: 99%

“…; Liu et al. ; Seifert & Xiong, ) has been interpreted as follows: Oct4A expression recognizes only cells with stem cell phenotype; Sox9, Pdx1, and Lgr5 expression recognize cells with both stem and progenitor cell phenotype; cells with Oct4A − /Sox9 + /Pdx1 + /Ngn3 − phenotype are considered pancreatic committed progenitor cells for both acinar and endocrine fates; Cells with an Oct4A − /Sox9 + /Pdx1 + /Ngn3 + phenotype are considered pancreatic endocrine progenitor cells.…”

Section: Methodsmentioning

confidence: 99%

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Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study

et al. 2015

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Pancreatic duct glands (PDGs) are tubule-alveolar glands associated with the pancreatic duct system and can be considered the anatomical counterpart of peribiliary glands (PBGs) 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 PBGs and of committed progenitors within PDGs. Here we have characterized more extensively the anatomy of human PDGs 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. PDGs 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 PDGs and were located primarily at the bottom of PDGs, 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, PDGs 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 PDGs 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.

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“…This interpretation corroborates the findings of others that there are no stem cells, only committed progenitors, in the pancreas postnatally (Zhou et al. ; Seifert & Xiong, ).…”

Section: Introductionsupporting

confidence: 92%

“…) and others (Zhou et al. ; Seifert & Xiong, ). A restricted Sox9 + sub‐population also expressed Ngn3, indicating features associated with the endocrine specification (Gomez et al.…”

Section: Discussionmentioning

confidence: 89%

“…; Wang et al. ; Seifert & Xiong, ). Therefore, nuclear, not cytoplasmic, expression of Oct4A was evaluated to identify true stem cells.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study

et al. 2015

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“…In Fbxw7-deleted pancreatic ducts, Ngn3 is activated and stabilized transcription of downstream effectors that regulate β cell differentiation. SCF Fbxw7 dominates the ubiquitination of regulatory proteins associated with cell cycle, cell growth, and cell fate [21]. Therefore, the reduction of pancreatic Fbxw7 has a key potential for ductal epithelia transdifferentiating to islet endocrine cells.…”

Section: Discussionmentioning

confidence: 99%

Immunophenotypes of Ductal Epithelial Cells in Advanced Pancreatic Ductal Adenocarcinoma

Zhou

Liu

et al. 2018

Digestion

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Background/Aims: In this report, we aimed to investigate the distribution and characterization of biomarker-immunolabeled ductal epithelium in advanced pancreatic ductal adenocarcinoma (PDAC). Design: Eighteen patients with PDAC were medically diagnosed prior to being treated periodically. All clinical records were collected and assayed. The PDAC samples were subjected to routine biochemical tests and immuno-stains of immunohistochemistry and immunofluorescence. Results: As results, immunohistochemical findings indicated pancreatic ductal cells in PDAC showed plenty of Ki-67, P53, RP, SAM positive cells expressed in nuclei. In addition, ductal epithelial cells exhibited numerous positive cells of CK7, 18, 19, 20 biomarkers, respectively. Interestingly, compared to non-PDAC controls, immunostaining results showed that endocrine hormones were positively expressed in pancreatic ducts of PDAC, characterized with increased insulin-, Ngn3-, PDX1-fluorescence-labeled cells, and reduced F-box and WD-40 domain protein 7 (Fbxw7)-labeled cells in ducts. Conclusion: These clinicopathologic findings preliminarily disclose that there may be a potential for insulin-producing cells in PDAC, possibly through negatively inducing Fbxw7 ubiquitination in pancreatic ducts.

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Degradation meets development: Implications in β‐cell development and diabetes

Ashok,

Kalthur,

Kumar

2024

Cell Biology International

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Pancreatic development is orchestrated by timely synthesis and degradation of stage‐specific transcription factors (TFs). The transition from one stage to another stage is dependent on the precise expression of the developmentally relevant TFs. Persistent expression of particular TF would impede the exit from the progenitor stage to the matured cell type. Intracellular protein degradation‐mediated protein turnover contributes to a major extent to the turnover of these TFs and thereby dictates the development of different tissues. Since even subtle changes in the crucial cellular pathways would dramatically impact pancreatic β‐cell performance, it is generally acknowledged that the biological activity of these pathways is tightly regulated by protein synthesis and degradation process. Intracellular protein degradation is executed majorly by the ubiquitin proteasome system (UPS) and Lysosomal degradation pathway. As more than 90% of the TFs are targeted to proteasomal degradation, this review aims to examine the crucial role of UPS in normal pancreatic β‐cell development and how dysfunction of these pathways manifests in metabolic syndromes such as diabetes. Such understanding would facilitate designing a faithful approach to obtain a therapeutic quality of β‐cells from stem cells.

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Out of the F-box: Reawakening the Pancreas

Cited by 7 publications

References 10 publications

Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study

Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study

Immunophenotypes of Ductal Epithelial Cells in Advanced Pancreatic Ductal Adenocarcinoma

Degradation meets development: Implications in β‐cell development and diabetes

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