Transitional cells in the regenerating pancreas

D. Gu; M.S. Lee; T. Krahl; N. Sarvetnick

Summary

We examined the spectrum of intermediate cell types in the regenerating pancreas as duct epithelial cells progressed through their differentiation pathway to become mature endocrine cells. The model used was transgenic mice in which the pancreatic islets continue to grow during adulthood, unlike normal mice whose islet cell formation ceases early in life. Because the intermediate cells migrated into islet-like clusters at specific locations, we propose a specific pathway for islet development. Endocrine cells are derived from duct cells co-expressing a duct cell antigen, carbonic anhydrase II (CA II) and an exocrine enzyme, amylase. The CA II/amylase cells become amylase/endocrine intermediate cells as they exited from their lumenal location. The abluminal amylase/endocrine cells continue to differentiate to multihormone-bearing young endocrine cells, which migrated to form clusters with other differentiating endocrine cells.

REFERENCES

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2. Hanahan D.,
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(1988) Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53, 295–308
OpenUrl CrossRef PubMed Web of Science
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OpenUrl PubMed
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2. Aanstoot H. J.,
3. Kranenburg G.,
4. Reinhard M.,
5. Visser W. J.,
6. Bruining G. J.
(1992) The midgestation human fetal pancreas contains cells coexpressing islet hormones. Dev. Biol 153, 368–375
OpenUrl CrossRef PubMed Web of Science
1. De Lisle R. C.,
2. Grendell J. H.,
3. Williams J. A.
(1990) Growing pancreatic acinar cells (postpancreatitis and fetal) express a ductal antigen. Pancreas 5, 381–388
OpenUrl PubMed Web of Science
1. De Lisle R. C.,
2. Logsdon D. C.
(1990) Pancreatic acinar cells in culture expression of acinar and ductal antigens in a growth-related manner. Eur. J. Cell Biol 51, 64–75
OpenUrl PubMed Web of Science
1. Deltour L.,
2. Leduque P.,
3. Paldi A.,
4. Ripoche M. A.,
5. Dubois P.,
6. Jami J.
(1991) Polyclonal origin of pancreatic islets in aggregation mouse chimaeras. Development 112, 1115–1121
OpenUrl Abstract
1. Dubois P. M.
(1989) Ontogeny of the endocrine pancreas. Horm. Res 32, 53–60
OpenUrl CrossRef PubMed
1. Green I. C.,
2. Seifi S. E.,
3. Perrin D.,
4. Howell S. L.
(1981) Cell replication in the islets of Langerhans of adult rats: effect of frequency, ovariectomy and treatment with steroid hormones. J. Endocr 88, 219–224
OpenUrl Abstract/FREE Full Text
1. Gu D.,
2. Sarvetnick N.
(1993) Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice. Development 118, 33–46
OpenUrl Abstract
1. Herrera P.-L.,
2. Huarte J.,
3. Sanvito F.,
4. Meda P.,
5. Orci L.,
6. Vassalli J.-D.
(1991) Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene. Development 113, 1257–1265
OpenUrl Abstract
1. Higuchi Y.,
2. Herrera P.,
3. Muniesa P.,
4. Huarte J.,
5. Belin D.,
6. Ohashi P.,
7. Aichele P.,
8. Orci L.,
9. Vassalli J.-D.,
10. Vassalli P.
(1992) Expression of a tumor necrosis factor in murine pancreatic B cells results in severe and permanent insulitis without evolution towards diabetes. J. Exp. Med 176, 1719–1731
OpenUrl Abstract/FREE Full Text
1. Le Douarin N. M.
(1988) On the origin of pancreatic endocrine cells. Cell 53, 169–171
OpenUrl CrossRef PubMed Web of Science
1. Madsen O. D.,
2. Larsson L. I.,
3. Rehfeld J. F.,
4. Schwartz T. W.,
5. Lernmark A.,
6. Labrecque A. D.,
7. Steiner D. F.
(1986) Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones. J. Cell Biol 103, 2025–2034
OpenUrl Abstract/FREE Full Text
1. Madsen O. D.,
2. Serup P.,
3. Karlsen C.,
4. Petersen H. V.,
5. Blume N.,
6. Andersen F. G.,
7. Jensen J.,
8. Michelsen B. K.
(1993) A tumour model for the study of islet cell differentiation. Biochem. Soc. Trans 21, 142–146
OpenUrl FREE Full Text
1. Melmed R. N.,
2. Benitez C. J.,
3. Holt S. J.
(1972) Intermediate cells of the pancreas 1. Ultrastructural characterization. J. Cell Sci 11, 449–475
OpenUrl Abstract/FREE Full Text
1. Nielsen J. H.,
2. Linde S.,
3. Weilinder B. S.,
4. Billestrup N.,
5. Medsen O. D.
(1989) Growth hormone is a growth factor for the differentiated pancreatic beta cell. Mol. Endocrinol 13, 165–173
1. Orci L.
(1988) Macro-and micro-domains in the endocrine pancreas. Diabetes 31, 538–565
OpenUrl Abstract/FREE Full Text
1. Pettengill O. S.,
2. Faris R. A.,
3. Bell R. H. J.,
4. Kuhlmann E. T.,
5. Longnecker D. S.
(1993) Derivation of ductlike cell lines from a transplantable acinar cell carcinoma of the rat pancreas. Am. J. Pathol 143, 292–303
OpenUrl PubMed Web of Science
1. Philippe J.,
2. Chick W. L.,
3. Habener J. F.
(1987) Multipotentialphenotypic expression of genes encoding peptide hormones in rat insulisnoma cell lines. J. Clin. Invest 79, 351–358
1. Rao M. S.,
2. Yeldandi A. V.,
3. Reddy J. K.
(1990) Stem cell potential of ductular and periductular cells in the adult rat pancreas. Cell Diff. Dev 29, 155–163
OpenUrl CrossRef PubMed Web of Science
1. Teitelman G.,
2. Alpert S.,
3. Polak J. M.,
4. Martinez A.,
5. Hanahan D.
(1993) Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. Development 118, 1031–1039
OpenUrl Abstract/FREE Full Text
1. Teitelman G.,
2. Lee J. K.,
3. Alpert S.
(1987) Expression of cell type-specific markers during pancreatic development in the mouse: implications for pancreatic cell lineages. Cell Tissue Res 250, 435–439
OpenUrl PubMed
1. Wessells N. K.,
2. Cohen J. H.
(1967) Early pancreas organogenesis: morphogenesis, tissue interaction, and mass effects. Dev. Biol 15, 237–270
OpenUrl CrossRef PubMed Web of Science
1. Wessells N. K.,
2. Evans J.
(1968) Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas. Dev. Biol 17, 413–446
OpenUrl CrossRef PubMed Web of Science

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Kathryn Virginia Anderson (1952-2020)

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[1] Alpert S.,
Hanahan D.,
Teitelman G.
(1988) Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53, 295–308
OpenUrl CrossRef PubMed Web of Science

[2] Alpert S.,

[3] Hanahan D.,

[4] Teitelman G.

[5] Boswald M.,
Harasim S.,
Maurer-Schultze B.
(1990) Tracer dose and availability time of thymidine and bromodeoxyuridine: application of bromodeoxyuridine in cell kinetic studies. Cell Tissue Kinet 23, 169–181
OpenUrl PubMed Web of Science

[6] Boswald M.,

[7] Harasim S.,

[8] Maurer-Schultze B.

[9] Davidson P. M.,
Campbell I. L.,
Oxbrow L.,
Hutson J. M.,
Harrison L. C.
(1989) Pancreatic beta cell proliferation in rabbits demonstrated by bromodeoxyuridine labeling. Pancreas 4, 594–600
OpenUrl PubMed

[10] Davidson P. M.,

[11] Campbell I. L.,

[12] Oxbrow L.,

[13] Hutson J. M.,

[14] Harrison L. C.

[15] de Krijger R. R.,
Aanstoot H. J.,
Kranenburg G.,
Reinhard M.,
Visser W. J.,
Bruining G. J.
(1992) The midgestation human fetal pancreas contains cells coexpressing islet hormones. Dev. Biol 153, 368–375
OpenUrl CrossRef PubMed Web of Science

[16] de Krijger R. R.,

[17] Aanstoot H. J.,

[18] Kranenburg G.,

[19] Reinhard M.,

[20] Visser W. J.,

[21] Bruining G. J.

[22] De Lisle R. C.,
Grendell J. H.,
Williams J. A.
(1990) Growing pancreatic acinar cells (postpancreatitis and fetal) express a ductal antigen. Pancreas 5, 381–388
OpenUrl PubMed Web of Science

[23] De Lisle R. C.,

[24] Grendell J. H.,

[25] Williams J. A.

[26] De Lisle R. C.,
Logsdon D. C.
(1990) Pancreatic acinar cells in culture expression of acinar and ductal antigens in a growth-related manner. Eur. J. Cell Biol 51, 64–75
OpenUrl PubMed Web of Science

[27] De Lisle R. C.,

[28] Logsdon D. C.

[29] Deltour L.,
Leduque P.,
Paldi A.,
Ripoche M. A.,
Dubois P.,
Jami J.
(1991) Polyclonal origin of pancreatic islets in aggregation mouse chimaeras. Development 112, 1115–1121
OpenUrl Abstract

[30] Deltour L.,

[31] Leduque P.,

[32] Paldi A.,

[33] Ripoche M. A.,

[34] Dubois P.,

[35] Jami J.

[36] Dubois P. M.
(1989) Ontogeny of the endocrine pancreas. Horm. Res 32, 53–60
OpenUrl CrossRef PubMed

[37] Dubois P. M.

[38] Green I. C.,
Seifi S. E.,
Perrin D.,
Howell S. L.
(1981) Cell replication in the islets of Langerhans of adult rats: effect of frequency, ovariectomy and treatment with steroid hormones. J. Endocr 88, 219–224
OpenUrl Abstract/FREE Full Text

[39] Green I. C.,

[40] Seifi S. E.,

[41] Perrin D.,

[42] Howell S. L.

[43] Gu D.,
Sarvetnick N.
(1993) Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice. Development 118, 33–46
OpenUrl Abstract

[44] Gu D.,

[45] Sarvetnick N.

[46] Herrera P.-L.,
Huarte J.,
Sanvito F.,
Meda P.,
Orci L.,
Vassalli J.-D.
(1991) Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene. Development 113, 1257–1265
OpenUrl Abstract

[47] Herrera P.-L.,

[48] Huarte J.,

[49] Sanvito F.,

[50] Meda P.,

[51] Orci L.,

[52] Vassalli J.-D.

[53] Higuchi Y.,
Herrera P.,
Muniesa P.,
Huarte J.,
Belin D.,
Ohashi P.,
Aichele P.,
Orci L.,
Vassalli J.-D.,
Vassalli P.
(1992) Expression of a tumor necrosis factor in murine pancreatic B cells results in severe and permanent insulitis without evolution towards diabetes. J. Exp. Med 176, 1719–1731
OpenUrl Abstract/FREE Full Text

[54] Higuchi Y.,

[55] Herrera P.,

[56] Muniesa P.,

[57] Huarte J.,

[58] Belin D.,

[59] Ohashi P.,

[60] Aichele P.,

[61] Orci L.,

[62] Vassalli J.-D.,

[63] Vassalli P.

[64] Le Douarin N. M.
(1988) On the origin of pancreatic endocrine cells. Cell 53, 169–171
OpenUrl CrossRef PubMed Web of Science

[65] Le Douarin N. M.

[66] Madsen O. D.,
Larsson L. I.,
Rehfeld J. F.,
Schwartz T. W.,
Lernmark A.,
Labrecque A. D.,
Steiner D. F.
(1986) Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones. J. Cell Biol 103, 2025–2034
OpenUrl Abstract/FREE Full Text

[67] Madsen O. D.,

[68] Larsson L. I.,

[69] Rehfeld J. F.,

[70] Schwartz T. W.,

[71] Lernmark A.,

[72] Labrecque A. D.,

[73] Steiner D. F.

[74] Madsen O. D.,
Serup P.,
Karlsen C.,
Petersen H. V.,
Blume N.,
Andersen F. G.,
Jensen J.,
Michelsen B. K.
(1993) A tumour model for the study of islet cell differentiation. Biochem. Soc. Trans 21, 142–146
OpenUrl FREE Full Text

[75] Madsen O. D.,

[76] Serup P.,

[77] Karlsen C.,

[78] Petersen H. V.,

[79] Blume N.,

[80] Andersen F. G.,

[81] Jensen J.,

[82] Michelsen B. K.

[83] Melmed R. N.,
Benitez C. J.,
Holt S. J.
(1972) Intermediate cells of the pancreas 1. Ultrastructural characterization. J. Cell Sci 11, 449–475
OpenUrl Abstract/FREE Full Text

[84] Melmed R. N.,

[85] Benitez C. J.,

[86] Holt S. J.

[87] Nielsen J. H.,
Linde S.,
Weilinder B. S.,
Billestrup N.,
Medsen O. D.
(1989) Growth hormone is a growth factor for the differentiated pancreatic beta cell. Mol. Endocrinol 13, 165–173

[88] Nielsen J. H.,

[89] Linde S.,

[90] Weilinder B. S.,

[91] Billestrup N.,

[92] Medsen O. D.

[93] Orci L.
(1988) Macro-and micro-domains in the endocrine pancreas. Diabetes 31, 538–565
OpenUrl Abstract/FREE Full Text

[94] Orci L.

[95] Pettengill O. S.,
Faris R. A.,
Bell R. H. J.,
Kuhlmann E. T.,
Longnecker D. S.
(1993) Derivation of ductlike cell lines from a transplantable acinar cell carcinoma of the rat pancreas. Am. J. Pathol 143, 292–303
OpenUrl PubMed Web of Science

[96] Pettengill O. S.,

[97] Faris R. A.,

[98] Bell R. H. J.,

[99] Kuhlmann E. T.,

[100] Longnecker D. S.

[101] Philippe J.,
Chick W. L.,
Habener J. F.
(1987) Multipotentialphenotypic expression of genes encoding peptide hormones in rat insulisnoma cell lines. J. Clin. Invest 79, 351–358

[102] Philippe J.,

[103] Chick W. L.,

[104] Habener J. F.

[105] Rao M. S.,
Yeldandi A. V.,
Reddy J. K.
(1990) Stem cell potential of ductular and periductular cells in the adult rat pancreas. Cell Diff. Dev 29, 155–163
OpenUrl CrossRef PubMed Web of Science

[106] Rao M. S.,

[107] Yeldandi A. V.,

[108] Reddy J. K.

[109] Teitelman G.,
Alpert S.,
Polak J. M.,
Martinez A.,
Hanahan D.
(1993) Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. Development 118, 1031–1039
OpenUrl Abstract/FREE Full Text

[110] Teitelman G.,

[111] Alpert S.,

[112] Polak J. M.,

[113] Martinez A.,

[114] Hanahan D.

[115] Teitelman G.,
Lee J. K.,
Alpert S.
(1987) Expression of cell type-specific markers during pancreatic development in the mouse: implications for pancreatic cell lineages. Cell Tissue Res 250, 435–439
OpenUrl PubMed

[116] Teitelman G.,

[117] Lee J. K.,

[118] Alpert S.

[119] Wessells N. K.,
Cohen J. H.
(1967) Early pancreas organogenesis: morphogenesis, tissue interaction, and mass effects. Dev. Biol 15, 237–270
OpenUrl CrossRef PubMed Web of Science

[120] Wessells N. K.,

[121] Cohen J. H.

[122] Wessells N. K.,
Evans J.
(1968) Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas. Dev. Biol 17, 413–446
OpenUrl CrossRef PubMed Web of Science

[123] Wessells N. K.,

[124] Evans J.

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Kathryn Virginia Anderson (1952-2020)

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Main menu

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Summary

REFERENCES

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Related articles

Cited by...

More in this TOC section

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Other journals from The Company of Biologists

Kathryn Virginia Anderson (1952-2020)

Zooming into 2021

Read & Publish participation extends worldwide

Upcoming special issues

Development presents...