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Article: PDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and differentiation of human fetal pancreatic progenitor cells

TitlePDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and differentiation of human fetal pancreatic progenitor cells
Authors
KeywordsDiabetes
Human fetus
Nestin
Pancreatic stem cells
PDZD2
Issue Date2008
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocel
Citation
International Journal Of Biochemistry And Cell Biology, 2008, v. 40 n. 4, p. 789-803 How to Cite?
AbstractEarly-trimester human fetal pancreas is a promising potential source of pancreatic progenitor cells. However, the ethical controversy associated with the source of these cells, and technical difficulties associated with their differentiation into insulin-producing cells have limited both their availability and utility. This study aimed to characterize a population of pancreatic progenitor cells (PPCs) isolated from human fetus and describe the effects of a novel factor, PDZ-domain containing-2 (PDZD2), and its secreted form (sPDZD2), on PPC proliferation and differentiation. In particular, we examined and characterized the expression of several stem cell (nestin, ABCG2, c-kit), growth and differentiation markers (GLP-1R, c-met, erbB1), and PDZD2 in PPCs by RT-PCR, Western blot, and immunocytochemistry. We also examined the effects of sPDZD2 on PPC proliferation and differentiation by examining BrdU incorporation, MTT, cell number, and real-time PCR as well as ELISA. PPCs were isolated, cultured and characterized from human fetal pancreas. PDZD2 and sPDZD2 were detected at high levels in both human fetal pancreas and in PPCs. sPDZD2 acted as a potent mitogen on PPCs, and inhibited the differentiation of PPC-derived islet-like cell-clusters (ICCs), evidenced by the downregulation of Isl-1, Pdx-1, and insulin mRNA levels. sPDZD2 treatment also reduced levels of C-peptide in ICCs. These results show that a novel pancreatic developmental factor, PDZD2, is sufficient to promote the proliferation of human fetal PPCs while limiting differentiation of ICCs into islet/endocrine cells. Findings from this study will contribute to the development of improved methods for islet transplantation therapy in the treatment of diabetes. © 2007 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/68144
ISSN
2023 Impact Factor: 3.4
2023 SCImago Journal Rankings: 1.079
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSuen, PMen_HK
dc.contributor.authorZou, Cen_HK
dc.contributor.authorZhang, YAen_HK
dc.contributor.authorLau, TKen_HK
dc.contributor.authorChan, Jen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorLeung, PSen_HK
dc.date.accessioned2010-09-06T06:01:47Z-
dc.date.available2010-09-06T06:01:47Z-
dc.date.issued2008en_HK
dc.identifier.citationInternational Journal Of Biochemistry And Cell Biology, 2008, v. 40 n. 4, p. 789-803en_HK
dc.identifier.issn1357-2725en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68144-
dc.description.abstractEarly-trimester human fetal pancreas is a promising potential source of pancreatic progenitor cells. However, the ethical controversy associated with the source of these cells, and technical difficulties associated with their differentiation into insulin-producing cells have limited both their availability and utility. This study aimed to characterize a population of pancreatic progenitor cells (PPCs) isolated from human fetus and describe the effects of a novel factor, PDZ-domain containing-2 (PDZD2), and its secreted form (sPDZD2), on PPC proliferation and differentiation. In particular, we examined and characterized the expression of several stem cell (nestin, ABCG2, c-kit), growth and differentiation markers (GLP-1R, c-met, erbB1), and PDZD2 in PPCs by RT-PCR, Western blot, and immunocytochemistry. We also examined the effects of sPDZD2 on PPC proliferation and differentiation by examining BrdU incorporation, MTT, cell number, and real-time PCR as well as ELISA. PPCs were isolated, cultured and characterized from human fetal pancreas. PDZD2 and sPDZD2 were detected at high levels in both human fetal pancreas and in PPCs. sPDZD2 acted as a potent mitogen on PPCs, and inhibited the differentiation of PPC-derived islet-like cell-clusters (ICCs), evidenced by the downregulation of Isl-1, Pdx-1, and insulin mRNA levels. sPDZD2 treatment also reduced levels of C-peptide in ICCs. These results show that a novel pancreatic developmental factor, PDZD2, is sufficient to promote the proliferation of human fetal PPCs while limiting differentiation of ICCs into islet/endocrine cells. Findings from this study will contribute to the development of improved methods for islet transplantation therapy in the treatment of diabetes. © 2007 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocelen_HK
dc.relation.ispartofInternational Journal of Biochemistry and Cell Biologyen_HK
dc.subjectDiabetes-
dc.subjectHuman fetus-
dc.subjectNestin-
dc.subjectPancreatic stem cells-
dc.subjectPDZD2-
dc.subject.meshAdaptor Proteins, Signal Transducing - genetics - metabolism - physiologyen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshC-Peptide - metabolismen_HK
dc.subject.meshCell Differentiation - genetics - physiologyen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshNeoplasm Proteins - genetics - metabolism - physiologyen_HK
dc.subject.meshPancreas - cytology - embryology - metabolismen_HK
dc.subject.meshRecombinant Proteins - metabolismen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.titlePDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and differentiation of human fetal pancreatic progenitor cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1357-2725&volume=40&spage=789&epage=803&date=2008&atitle=PDZ-domain+containing-2+(PDZD2)+is+a+novel+factor+that+affects+the+growth+and+differentiation+of+human+fetal+pancreatic+progenitor+cellsen_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.biocel.2007.10.020en_HK
dc.identifier.pmid18037333-
dc.identifier.scopuseid_2-s2.0-39649092092en_HK
dc.identifier.hkuros144993en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-39649092092&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume40en_HK
dc.identifier.issue4en_HK
dc.identifier.spage789en_HK
dc.identifier.epage803en_HK
dc.identifier.isiWOS:000254602600022-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridSuen, PM=6701661375en_HK
dc.identifier.scopusauthoridZou, C=35972843000en_HK
dc.identifier.scopusauthoridZhang, YA=7601309729en_HK
dc.identifier.scopusauthoridLau, TK=40261882800en_HK
dc.identifier.scopusauthoridChan, J=7403286662en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridLeung, PS=7401748938en_HK
dc.identifier.issnl1357-2725-

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