Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice

Angela Criscimanna, Julie A. Speicher, Golbahar Houshmand, Chiyo Shiota, Krishna Prasadan, Baoan D Ji, Craig D. Logsdon, George K. Gittes, Farzad Esni

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Background & Aims: There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response. Methods: To target specific types of pancreatic cells, we crossed R26 DTR or R26 DTR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters. Results: Exposure of PdxCre;R26 DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCreERT2;R26 DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage. Conclusions: In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process.

Original languageEnglish (US)
JournalGastroenterology
Volume141
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Endocrine Cells
Acinar Cells
Regeneration
Pancreas
Wounds and Injuries
Diphtheria Toxin
Population Control
Pancreatic Elastase
Transgenic Mice
Theoretical Models
Stem Cells
Epithelial Cells
Heparin-binding EGF-like Growth Factor

Keywords

  • β-Cell
  • Mouse Model
  • Organogenesis
  • Tissue Repair

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice. / Criscimanna, Angela; Speicher, Julie A.; Houshmand, Golbahar; Shiota, Chiyo; Prasadan, Krishna; Ji, Baoan D; Logsdon, Craig D.; Gittes, George K.; Esni, Farzad.

In: Gastroenterology, Vol. 141, No. 4, 10.2011.

Research output: Contribution to journalArticle

Criscimanna, A, Speicher, JA, Houshmand, G, Shiota, C, Prasadan, K, Ji, BD, Logsdon, CD, Gittes, GK & Esni, F 2011, 'Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice', Gastroenterology, vol. 141, no. 4. https://doi.org/10.1053/j.gastro.2011.07.003
Criscimanna, Angela ; Speicher, Julie A. ; Houshmand, Golbahar ; Shiota, Chiyo ; Prasadan, Krishna ; Ji, Baoan D ; Logsdon, Craig D. ; Gittes, George K. ; Esni, Farzad. / Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice. In: Gastroenterology. 2011 ; Vol. 141, No. 4.
@article{5087fd5f389b4e198053814e2b5a0e60,
title = "Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice",
abstract = "Background & Aims: There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response. Methods: To target specific types of pancreatic cells, we crossed R26 DTR or R26 DTR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters. Results: Exposure of PdxCre;R26 DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCreERT2;R26 DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage. Conclusions: In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process.",
keywords = "β-Cell, Mouse Model, Organogenesis, Tissue Repair",
author = "Angela Criscimanna and Speicher, {Julie A.} and Golbahar Houshmand and Chiyo Shiota and Krishna Prasadan and Ji, {Baoan D} and Logsdon, {Craig D.} and Gittes, {George K.} and Farzad Esni",
year = "2011",
month = "10",
doi = "10.1053/j.gastro.2011.07.003",
language = "English (US)",
volume = "141",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice

AU - Criscimanna, Angela

AU - Speicher, Julie A.

AU - Houshmand, Golbahar

AU - Shiota, Chiyo

AU - Prasadan, Krishna

AU - Ji, Baoan D

AU - Logsdon, Craig D.

AU - Gittes, George K.

AU - Esni, Farzad

PY - 2011/10

Y1 - 2011/10

N2 - Background & Aims: There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response. Methods: To target specific types of pancreatic cells, we crossed R26 DTR or R26 DTR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters. Results: Exposure of PdxCre;R26 DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCreERT2;R26 DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage. Conclusions: In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process.

AB - Background & Aims: There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response. Methods: To target specific types of pancreatic cells, we crossed R26 DTR or R26 DTR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters. Results: Exposure of PdxCre;R26 DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCreERT2;R26 DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage. Conclusions: In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process.

KW - β-Cell

KW - Mouse Model

KW - Organogenesis

KW - Tissue Repair

UR - http://www.scopus.com/inward/record.url?scp=80053603426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053603426&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2011.07.003

DO - 10.1053/j.gastro.2011.07.003

M3 - Article

C2 - 21763240

AN - SCOPUS:80053603426

VL - 141

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 4

ER -