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

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.

Notch Signaling Is Involved in Neurogenic Commitment of Human Periodontal Ligament-Derived Mesenchymal Stem Cells

“…However, the protein expression was not observed by immunocytochemistry staining. In addition, it has been identified that periodontal ligament tissues contained a subpopulation that is derived from neural crest cells [10,25,26]. Thus, these cells may contain the intrinsic characteristics of neuroectodermal lineage.…”

Glycoprotein asporin as a novel player in tumour microenvironment and cancer progression

“…ASPN and anti-proliferative IGFBP5 (insulin-like growth factor binding protein) were up-regulated by transcription factor TonEBP (tonicity-responsive enhancer binding protein) in mouse embryonic fibroblasts and may be involved in renal adaptation to hypertonic stress 40 . Co-regulation of ASPN and IGFBP5 was also observed in alveolar bone osteoblasts 33 . Schaeffer et al 42 focused on gene expression in the murine prostate rudiment at three time points during the first 48 h of exposure to androgen, which initiates proliferation and invasion of prostate epithelial buds into surrounding urogenital sinus mesenchyme.…”

“…Another study showed that expression of ASPN, TGF-β1, and TGF-β3 (transforming factor beta) in osteoblasts from subchondral bone and in particular osteophytes of osteoarthritic patients was higher than that of non-osteoarthritic patients 32 . High ASPN expression was also found in alveolar bone osteoblasts 33 . The family of small leucine rich repeat proteoglycans is commonly found in cartilage tissues where ASPN competes with other SLRPs in many processes 34 .…”

“…With respect to histone methylation, high expression of ASPN was found in alveolar bone osteoblasts with high levels of H3K9me3 (ref. 33 ), but global loss of H3K9 trimethylation has been observed in several cancers 52 . …”

Stem cells in dentistry – Review of literature

“…Neural crests are multipotent cells with a high regenerative capacity (Rinon et al 2011). They play a vital role in tooth development by inducing the growth of the mesenchymal component, including odontoblasts, dental pulp, apical vessels and periodontal ligaments (Dangaria et al 2011). SHEDs have the same molecular properties as neural crests and stem cells.…”