Identification of markers for newly formed beta-cells in the perinatal period: a time of recognized beta-cell immaturity.
Markers of beta-cell maturity would be useful in staging the differentiation of stem/progenitor cells to beta-cells whether in vivo or in vitro. We previously identified markers for newly formed beta-cells in regenerating rat pancreases after 90% partial pancreatectomy. To test the generality of these markers of newly formed beta-cells, we examined their expression during the perinatal period, a time of recognized beta-cell immaturity. We show by semiquantitative RT-PCR and immunostaining over the time course from embryonic day 18/20 to birth, 1 day, 2 days, 3 days, 7 days, and adult that MMP-2, CK-19, and SPD are truly markers of new and immature beta-cells and that their expression transiently peaks in the perinatal period and is not entirely synchronous. The shared expression of these markers among fetal, newborn, and newly regenerated beta-cells, but not adult, strongly supports their use as potential markers for new beta-cells in the assessment of both the maturity of stem cell-derived insulin-producing cells and the presence of newly formed islets (neogenesis) in the adult pancreas.
Aye
Tandy
T
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Toschi
Elena
E
Sharma
Arun
A
Sgroi
Dennis
D
Bonner-Weir
Susan
S
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D053539:Keratin-19 / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; D053539:Keratin-19; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2