Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro
To gain more understanding of the complex molecular processes underlying cleft lip/palate (CLP), we established a unique human cell bank, consisting of keratinocytes and corresponding fibroblasts from individual CLP patients as a new study tool. After their careful characterization, we used such pat...
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doaj-719d1874c1024f5f9138cf33aa3ca9502020-11-24T22:05:44ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-11-01910.3389/fphys.2018.01703422351Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitroMartin Degen0Astrid Wiederkehr1Giorgio C. La Scala2Christina Carmann3Isabelle Schnyder4Christos Katsaros5Laboratory for Oral Molecular Biology, Department of Orthodontics and Dentofacial Orthopedics, University of Bern, Bern, SwitzerlandLaboratory for Oral Molecular Biology, Department of Orthodontics and Dentofacial Orthopedics, University of Bern, Bern, SwitzerlandDivision of Pediatric Surgery, Department of Pediatrics, Geneva University Hospitals, Geneva, SwitzerlandUniversity Clinic for Pediatric Surgery, Bern University Hospital, Bern, SwitzerlandUniversity Clinic for Pediatric Surgery, Bern University Hospital, Bern, SwitzerlandLaboratory for Oral Molecular Biology, Department of Orthodontics and Dentofacial Orthopedics, University of Bern, Bern, SwitzerlandTo gain more understanding of the complex molecular processes underlying cleft lip/palate (CLP), we established a unique human cell bank, consisting of keratinocytes and corresponding fibroblasts from individual CLP patients as a new study tool. After their careful characterization, we used such patient-derived cell cultures as well as control keratinocytes for in vitro differentiation and proliferation assays. Foreskin-derived control cells as a group showed significant higher induction of the late differentiation markers Loricrin and Filaggrin than the group of CLP patients-derived keratinocytes. Additionally, we detected great variations between individual CLP keratinocyte cell cultures in regard to their potential to terminally differentiate as assessed by the induction of Loricrin and Filaggrin. Primary patient cell cultures that did not properly differentiate, exhibited high proliferation rates. Moreover, we could correlate the expression levels of transcription factor IRF6 to the ability of individual cell cultures to terminally differentiate. Using clinically relevant, patient-derived cells, our results suggest that some of the genetic predispositions causing CLP might also lead to deficiencies in keratinocyte differentiation manifested in in vitro assays.https://www.frontiersin.org/article/10.3389/fphys.2018.01703/fullcleft lip/palatekeratinocytesdifferentiationIRF6van der Woude Syndrome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martin Degen Astrid Wiederkehr Giorgio C. La Scala Christina Carmann Isabelle Schnyder Christos Katsaros |
spellingShingle |
Martin Degen Astrid Wiederkehr Giorgio C. La Scala Christina Carmann Isabelle Schnyder Christos Katsaros Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro Frontiers in Physiology cleft lip/palate keratinocytes differentiation IRF6 van der Woude Syndrome |
author_facet |
Martin Degen Astrid Wiederkehr Giorgio C. La Scala Christina Carmann Isabelle Schnyder Christos Katsaros |
author_sort |
Martin Degen |
title |
Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro |
title_short |
Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro |
title_full |
Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro |
title_fullStr |
Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro |
title_full_unstemmed |
Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro |
title_sort |
keratinocytes isolated from individual cleft lip/palate patients display variations in their differentiation potential in vitro |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2018-11-01 |
description |
To gain more understanding of the complex molecular processes underlying cleft lip/palate (CLP), we established a unique human cell bank, consisting of keratinocytes and corresponding fibroblasts from individual CLP patients as a new study tool. After their careful characterization, we used such patient-derived cell cultures as well as control keratinocytes for in vitro differentiation and proliferation assays. Foreskin-derived control cells as a group showed significant higher induction of the late differentiation markers Loricrin and Filaggrin than the group of CLP patients-derived keratinocytes. Additionally, we detected great variations between individual CLP keratinocyte cell cultures in regard to their potential to terminally differentiate as assessed by the induction of Loricrin and Filaggrin. Primary patient cell cultures that did not properly differentiate, exhibited high proliferation rates. Moreover, we could correlate the expression levels of transcription factor IRF6 to the ability of individual cell cultures to terminally differentiate. Using clinically relevant, patient-derived cells, our results suggest that some of the genetic predispositions causing CLP might also lead to deficiencies in keratinocyte differentiation manifested in in vitro assays. |
topic |
cleft lip/palate keratinocytes differentiation IRF6 van der Woude Syndrome |
url |
https://www.frontiersin.org/article/10.3389/fphys.2018.01703/full |
work_keys_str_mv |
AT martindegen keratinocytesisolatedfromindividualcleftlippalatepatientsdisplayvariationsintheirdifferentiationpotentialinvitro AT astridwiederkehr keratinocytesisolatedfromindividualcleftlippalatepatientsdisplayvariationsintheirdifferentiationpotentialinvitro AT giorgioclascala keratinocytesisolatedfromindividualcleftlippalatepatientsdisplayvariationsintheirdifferentiationpotentialinvitro AT christinacarmann keratinocytesisolatedfromindividualcleftlippalatepatientsdisplayvariationsintheirdifferentiationpotentialinvitro AT isabelleschnyder keratinocytesisolatedfromindividualcleftlippalatepatientsdisplayvariationsintheirdifferentiationpotentialinvitro AT christoskatsaros keratinocytesisolatedfromindividualcleftlippalatepatientsdisplayvariationsintheirdifferentiationpotentialinvitro |
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