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Article: PDZ-domain containing-2 (PDZD2) drives the maturity of human fetal pancreatic progenitor-derived islet-like cell clusters with functional responsiveness against membrane depolarization

TitlePDZ-domain containing-2 (PDZD2) drives the maturity of human fetal pancreatic progenitor-derived islet-like cell clusters with functional responsiveness against membrane depolarization
Authors
Issue Date2009
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/jht
Citation
Stem Cells And Development, 2009, v. 18 n. 7, p. 979-989 How to Cite?
AbstractWe recently reported the isolation and characterization of a population of pancreatic progenitor cells (PPCs) from early trimester human fetal pancreata. The PPCs, being the forerunners of adult pancreatic cell lineages, were amenable to growth and differentiation into insulin-secreting islet-like cell clusters (ICCs) upon stimulation by adequate morphogens. Of note, a novel morphogenic factor, PDZ-domain containing-2 (PDZD2) and its secreted form (sPDZD2) were ubiquitously expressed in the PPCs. Our goals for this study were to evaluate the potential role of sPDZD2 in stimulating PPC differentiation and to establish the optimal concentration for such stimulation. We found that 10-9M sPDZD2 promoted PPC differentiation, as evidenced by the upregulation of the pancreatic endocrine markers (PDX-1, NGN3, NEURO-D, ISL-1, NKX 2.2, NKX 6.1) and INSULIN mRNA. Inhibited endogenous production of sPDZD2 suppressed expression of these factors. Secreted PDZD2 treatment significantly elevated the C-peptide content of the ICCs and increased the basal rate of insulin secretion. However, they remained unresponsive to glucose stimulation, reflected by a minimal increase in GLUT-2 and GLUCOKINASE mRNA expression. Interestingly, sPDZD2 treatment induced increased expression of the L-type voltage-gated calcium channel (Cav1.2) in the ICCs, triggering calcium ion influx under KCl stimulation and conferring an ability to secrete insulin in response to KCl. Pancreatic progenitor cells from 10- and 13-week fetal pancreata showed peak expression of endogenous sPDZD2, implying that sPDZD2 has a specific role in islet development during the first trimester. In conclusion, our data suggest that sPDZD2 promotes functional maturation of human fetal PPC-derived ICCs, thus enhancing its transplanting potentials. © 2009 Mary Ann Liebert, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/58273
ISSN
2015 Impact Factor: 3.777
2015 SCImago Journal Rankings: 1.703
ISI Accession Number ID
Funding AgencyGrant Number
Li Ka Shing Institute of Health Sciences6901987
Research Grants Council of Hong KongCUHK 4537/05M
Funding Information:

We gratefully acknowledge financial support provided by the Li Ka Shing Institute of Health Sciences (Project Code: 6901987, awarded to P. S. L.) and the Research Grants Council of Hong Kong (Competitive Earmarked Research Grant CUHK 4537/05M awarded to P. S. L.). We thank Wallace C. Y. Yip for his excellent technical support with calcium imaging analysis, and we also thank Dr. Shannon W. N. Au for the technical support of the synthesis of recombinant sPDZD2 peptide.

References

 

DC FieldValueLanguage
dc.contributor.authorLeung, KKen_HK
dc.contributor.authorSuen, PMen_HK
dc.contributor.authorLau, TKen_HK
dc.contributor.authorKo, WHen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorLeung, PSen_HK
dc.date.accessioned2010-05-31T03:27:13Z-
dc.date.available2010-05-31T03:27:13Z-
dc.date.issued2009en_HK
dc.identifier.citationStem Cells And Development, 2009, v. 18 n. 7, p. 979-989en_HK
dc.identifier.issn1547-3287en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58273-
dc.description.abstractWe recently reported the isolation and characterization of a population of pancreatic progenitor cells (PPCs) from early trimester human fetal pancreata. The PPCs, being the forerunners of adult pancreatic cell lineages, were amenable to growth and differentiation into insulin-secreting islet-like cell clusters (ICCs) upon stimulation by adequate morphogens. Of note, a novel morphogenic factor, PDZ-domain containing-2 (PDZD2) and its secreted form (sPDZD2) were ubiquitously expressed in the PPCs. Our goals for this study were to evaluate the potential role of sPDZD2 in stimulating PPC differentiation and to establish the optimal concentration for such stimulation. We found that 10-9M sPDZD2 promoted PPC differentiation, as evidenced by the upregulation of the pancreatic endocrine markers (PDX-1, NGN3, NEURO-D, ISL-1, NKX 2.2, NKX 6.1) and INSULIN mRNA. Inhibited endogenous production of sPDZD2 suppressed expression of these factors. Secreted PDZD2 treatment significantly elevated the C-peptide content of the ICCs and increased the basal rate of insulin secretion. However, they remained unresponsive to glucose stimulation, reflected by a minimal increase in GLUT-2 and GLUCOKINASE mRNA expression. Interestingly, sPDZD2 treatment induced increased expression of the L-type voltage-gated calcium channel (Cav1.2) in the ICCs, triggering calcium ion influx under KCl stimulation and conferring an ability to secrete insulin in response to KCl. Pancreatic progenitor cells from 10- and 13-week fetal pancreata showed peak expression of endogenous sPDZD2, implying that sPDZD2 has a specific role in islet development during the first trimester. In conclusion, our data suggest that sPDZD2 promotes functional maturation of human fetal PPC-derived ICCs, thus enhancing its transplanting potentials. © 2009 Mary Ann Liebert, Inc.en_HK
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/jhten_HK
dc.relation.ispartofStem Cells and Developmenten_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - biosynthesis - pharmacologyen_HK
dc.subject.meshAntigens, Differentiation - biosynthesisen_HK
dc.subject.meshC-Peptide - metabolismen_HK
dc.subject.meshCalcium - metabolismen_HK
dc.subject.meshCalcium Channels, L-Type - metabolismen_HK
dc.subject.meshCell Differentiation - drug effects - physiologyen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshFetus - cytology - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInsulin - secretionen_HK
dc.subject.meshInsulin-Secreting Cells - cytology - metabolismen_HK
dc.subject.meshIon Transport - drug effects - physiologyen_HK
dc.subject.meshMembrane Potentials - drug effects - physiologyen_HK
dc.subject.meshNeoplasm Proteins - biosynthesis - pharmacologyen_HK
dc.subject.meshPotassium Chloride - pharmacologyen_HK
dc.subject.meshStem Cells - cytology - metabolismen_HK
dc.subject.meshUp-Regulation - drug effects - physiologyen_HK
dc.titlePDZ-domain containing-2 (PDZD2) drives the maturity of human fetal pancreatic progenitor-derived islet-like cell clusters with functional responsiveness against membrane depolarizationen_HK
dc.typeArticleen_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1089/scd.2008.0325en_HK
dc.identifier.pmid19046020-
dc.identifier.scopuseid_2-s2.0-70349414656en_HK
dc.identifier.hkuros157214en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349414656&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue7en_HK
dc.identifier.spage979en_HK
dc.identifier.epage989en_HK
dc.identifier.eissn1557-8534-
dc.identifier.isiWOS:000269701000004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, KK=24399488000en_HK
dc.identifier.scopusauthoridSuen, PM=6701661375en_HK
dc.identifier.scopusauthoridLau, TK=40261882800en_HK
dc.identifier.scopusauthoridKo, WH=15042661000en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridLeung, PS=7401748938en_HK

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