TY - JOUR
T1 - Endocrine precursor cells from mouse islets are not generated by epithelial-to-mesenchymal transition of mature beta cells
AU - Morton, Russell A.
AU - Geras-Raaka, Elizabeth
AU - Wilson, Leah M.
AU - Raaka, Bruce M.
AU - Gershengorn, Marvin C.
N1 - Funding Information:
This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. We thank Graeme Bell and Manami Hara for providing MIP-GFP transgenic mice, Douglas Melton for providing RIP/CreER mice and Jurgen Wess for providing beta cell-specific M 3 muscarinic receptor knockout mice, and Yuval Dor and Shimon Efrat for helpful discussions.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - We previously presented evidence that proliferative human islet precursor cells may be derived in vitro from adult islets by epithelial-to-mesenchymal transition (EMT) and show here that similar fibroblast-like cells can be derived from mouse islets. These mouse cell populations exhibited changes in gene expression consistent with EMT. Both C-peptide and insulin mRNAs were undetectable in expanded cultures of mouse islet-derived precursor cells (mIPCs). After expansion, mIPCs could be induced to migrate into clusters and differentiate into hormone-expressing islet-like aggregates. Although early morphological changes suggesting EMT were observed by time-lapse microscopy when green fluorescent protein-labeled beta cells were placed in culture, the expanded precursor cell population was not fluorescent. Using two mouse models in which beta cells were permanently made either to express alkaline phosphatase or to have a deleted M3 muscarinic receptor, we provide evidence that mIPCs in long term culture are not derived from beta cells.
AB - We previously presented evidence that proliferative human islet precursor cells may be derived in vitro from adult islets by epithelial-to-mesenchymal transition (EMT) and show here that similar fibroblast-like cells can be derived from mouse islets. These mouse cell populations exhibited changes in gene expression consistent with EMT. Both C-peptide and insulin mRNAs were undetectable in expanded cultures of mouse islet-derived precursor cells (mIPCs). After expansion, mIPCs could be induced to migrate into clusters and differentiate into hormone-expressing islet-like aggregates. Although early morphological changes suggesting EMT were observed by time-lapse microscopy when green fluorescent protein-labeled beta cells were placed in culture, the expanded precursor cell population was not fluorescent. Using two mouse models in which beta cells were permanently made either to express alkaline phosphatase or to have a deleted M3 muscarinic receptor, we provide evidence that mIPCs in long term culture are not derived from beta cells.
KW - Beta cells
KW - Epithelial-to-mesenchymal transition
KW - Genetically marked beta cells
KW - Human islet-derived precursor cells
KW - Insulin
KW - Islet hormones
KW - Mouse islet-derived precursor cells
KW - Transgenic mouse models
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U2 - 10.1016/j.mce.2007.02.005
DO - 10.1016/j.mce.2007.02.005
M3 - Article
C2 - 17363142
AN - SCOPUS:34247589600
SN - 0303-7207
VL - 270
SP - 87
EP - 93
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -