Abstract
Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3767-3776 |
| Number of pages | 10 |
| Journal | Development |
| Volume | 132 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 2005 |
Fingerprint
Keywords
- Cancer
- Differentiation
- Metaplasia
- Mouse
- Pancreas
- Stem cells
- TGFα
- Transdifferentiation
ASJC Scopus subject areas
- Anatomy
- Cell Biology
Cite this
Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. / Means, Anna L.; Meszoely, Ingrid M.; Suzuki, Kazufumi; Miyamoto, Yoshiharu; Rustgi, Anil K.; Coffey, Robert J.; Wright, Christopher V E; Stoffers, Doris A.; Leach, Steven D.
In: Development, Vol. 132, No. 16, 08.2005, p. 3767-3776.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates
AU - Means, Anna L.
AU - Meszoely, Ingrid M.
AU - Suzuki, Kazufumi
AU - Miyamoto, Yoshiharu
AU - Rustgi, Anil K.
AU - Coffey, Robert J.
AU - Wright, Christopher V E
AU - Stoffers, Doris A.
AU - Leach, Steven D.
PY - 2005/8
Y1 - 2005/8
N2 - Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.
AB - Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.
KW - Cancer
KW - Differentiation
KW - Metaplasia
KW - Mouse
KW - Pancreas
KW - Stem cells
KW - TGFα
KW - Transdifferentiation
UR - http://www.scopus.com/inward/record.url?scp=24944441782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24944441782&partnerID=8YFLogxK
U2 - 10.1242/dev.01925
DO - 10.1242/dev.01925
M3 - Article
C2 - 16020518
AN - SCOPUS:24944441782
VL - 132
SP - 3767
EP - 3776
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 16
ER -