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Differentiation of Neural-Crest-Derived Intermediate Pluripotent Progenitors into Committed Periodontal Populations Involves Unique Molecular Signature Changes, Cohort Shifts, and Epigenetic Modifications

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Title: Differentiation of Neural-Crest-Derived Intermediate Pluripotent Progenitors into Committed Periodontal Populations Involves Unique Molecular Signature Changes, Cohort Shifts, and Epigenetic Modifications
Author(s): Dangaria, Smit J.; Ito, Yoshihiro; Luan, Xianghong; Diekwisch, Thomas G.H.
Subject(s): Intermediate progenitor populations cranial neural crest
Abstract: Intermediate progenitor populations play a crucial role in the regional specification and differentiation of the cranial neural crest. On the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, we have defined key factors involved in the differentiation of dental follicle (DF) intermediate progenitors into periodontal lineages, including alveolar bone (AB) osteoblasts, cementoblasts, and periodontal ligament (PDL) cells. When comparing differentially expressed genes, PDL cells most closely resembled DF progenitors, followed by AB osteoblasts and cementoblasts as the most distant population. According to gene ontology analyses, extracellular matrix-adhesion proteins were substantially increased in PDL cells, osteogenesis factors were elevated in AB osteoblasts, and gene expression levels were lower in cementoblasts, especially in the cytokine group. Unique signature proteins included interleukin 6, paired-like homeodomain transcription factor 2, thrombospondin 2, and glial cell line-derived neurotrophic factor for DF progenitors; asporin and prostaglandin-H2 D-isomerase for AB osteoblasts; and keratin 18, Netrin 4, Jagged 1, and Dickkopf1 for cementoblasts, as verified by western blot analysis. Secreted frizzled-related protein 1 was preferentially expressed in PDL cells, whereas matrix Gla-protein, bone sialoprotein, and insulin-like growth factor binding protein 5 were higher in AB osteoblasts than in cementoblasts. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Together, our data indicate that in addition to changes in signature gene expression, unique shifts in gene cohort expression levels, epigenetic modifications, and changes in cell morphology contribute to the individuation of tissue populations from a common neural-crest-derived ancestor.
Issue Date: 2011-01
Publisher: Mary Ann Liebert
Citation Info: Dangaria, S. J., Ito, Y., Luan, X. H., & Diekwisch, T. G. H. 2011. Differentiation of Neural-Crest-Derived Intermediate Pluripotent Progenitors into Committed Periodontal Populations Involves Unique Molecular Signature Changes, Cohort Shifts, and Epigenetic Modifications. Stem Cells and Development, 20(1): 39-52. DOI: 10.1089/scd.2010.0180
Type: Article
Description: This is a copy of an article published in Stem Cells and Development © 2011 [Copyright Mary Ann Liebert, Inc.]; Stem Cells and Development is available online at: http://www.liebertonline.com. DOI: 10.1089/scd.2010.0180.
URI: http://hdl.handle.net/10027/7759
ISSN: 1547-3287
Sponsor: Generous support for these studies by NIDCR grant DE15425 is gratefully acknowledged.
Date Available in INDIGO: 2011-05-27
 

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