Pancreatic stem cells originate during the pancreatic progenitor developmental stage

Previously isolated adult pancreatic precursors called pancreatic multipotent progenitors (which make both pancreatic endocrine and exocrine cell types) originate from the Pancreatic Duodenal Homeobox 1 (PDX1) pancreatic developmental lineage. The embryonic time point at which adult pancreatic multi...

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Main Authors: Krystal Jacques, Brenda L. K. Coles, Derek van der Kooy
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1521411/full
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author Krystal Jacques
Krystal Jacques
Brenda L. K. Coles
Brenda L. K. Coles
Derek van der Kooy
Derek van der Kooy
Derek van der Kooy
author_facet Krystal Jacques
Krystal Jacques
Brenda L. K. Coles
Brenda L. K. Coles
Derek van der Kooy
Derek van der Kooy
Derek van der Kooy
author_sort Krystal Jacques
collection DOAJ
description Previously isolated adult pancreatic precursors called pancreatic multipotent progenitors (which make both pancreatic endocrine and exocrine cell types) originate from the Pancreatic Duodenal Homeobox 1 (PDX1) pancreatic developmental lineage. The embryonic time point at which adult pancreatic multipotent progenitor cells emerge has not been established. We have employed the use of two models: a human embryonic stem cell (hESC) to beta-cell cytokine-induced differentiation protocol and a mouse lineage tracing model during early development to isolate clonal pancreatic spheres. The results show that insulin-positive clonal spheres can be isolated as early as the pancreatic endoderm stage as well as the pancreatic progenitor stage during the hESC to beta-cell lineage differentiation model and that they can be isolated only as early as the pancreatic progenitor stage during mouse embryogenesis. Further, pancreatic clonal sphere-forming cells isolated from the pancreatic progenitor stage in embryonic mice display multipotentiality, and those isolated at a later gestational age demonstrate self-renewal ability. These findings suggest that pancreatic precursors isolated from mouse embryonic time points have stem cell properties and that the pancreatic progenitor stage in hESC development may be the optimal time to capture and expand these stem cells and make large numbers of beta cells.
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spelling doaj-art-e5d31975e6664513a2d331face9c990f2025-08-20T03:01:03ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-02-011310.3389/fcell.2025.15214111521411Pancreatic stem cells originate during the pancreatic progenitor developmental stageKrystal Jacques0Krystal Jacques1Brenda L. K. Coles2Brenda L. K. Coles3Derek van der Kooy4Derek van der Kooy5Derek van der Kooy6Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaDonnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaPreviously isolated adult pancreatic precursors called pancreatic multipotent progenitors (which make both pancreatic endocrine and exocrine cell types) originate from the Pancreatic Duodenal Homeobox 1 (PDX1) pancreatic developmental lineage. The embryonic time point at which adult pancreatic multipotent progenitor cells emerge has not been established. We have employed the use of two models: a human embryonic stem cell (hESC) to beta-cell cytokine-induced differentiation protocol and a mouse lineage tracing model during early development to isolate clonal pancreatic spheres. The results show that insulin-positive clonal spheres can be isolated as early as the pancreatic endoderm stage as well as the pancreatic progenitor stage during the hESC to beta-cell lineage differentiation model and that they can be isolated only as early as the pancreatic progenitor stage during mouse embryogenesis. Further, pancreatic clonal sphere-forming cells isolated from the pancreatic progenitor stage in embryonic mice display multipotentiality, and those isolated at a later gestational age demonstrate self-renewal ability. These findings suggest that pancreatic precursors isolated from mouse embryonic time points have stem cell properties and that the pancreatic progenitor stage in hESC development may be the optimal time to capture and expand these stem cells and make large numbers of beta cells.https://www.frontiersin.org/articles/10.3389/fcell.2025.1521411/fullpancreatic progenitorpancreatic developmentclonal assayshuman ES cell differentiationmouse primary cell culturebeta cell (β cell)
spellingShingle Krystal Jacques
Krystal Jacques
Brenda L. K. Coles
Brenda L. K. Coles
Derek van der Kooy
Derek van der Kooy
Derek van der Kooy
Pancreatic stem cells originate during the pancreatic progenitor developmental stage
Frontiers in Cell and Developmental Biology
pancreatic progenitor
pancreatic development
clonal assays
human ES cell differentiation
mouse primary cell culture
beta cell (β cell)
title Pancreatic stem cells originate during the pancreatic progenitor developmental stage
title_full Pancreatic stem cells originate during the pancreatic progenitor developmental stage
title_fullStr Pancreatic stem cells originate during the pancreatic progenitor developmental stage
title_full_unstemmed Pancreatic stem cells originate during the pancreatic progenitor developmental stage
title_short Pancreatic stem cells originate during the pancreatic progenitor developmental stage
title_sort pancreatic stem cells originate during the pancreatic progenitor developmental stage
topic pancreatic progenitor
pancreatic development
clonal assays
human ES cell differentiation
mouse primary cell culture
beta cell (β cell)
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1521411/full
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