Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament

Abstract

Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. This study identified periodontal ligament associated protein-1 (Plap-1) as a PDL-specific extracellular matrix protein. We generated knock-in mice expressing CreERT2 and GFP specifically in Plap-1-positive PDLCs. Genetic lineage tracing confirmed the long-standing hypothesis that PDLCs differentiate into osteoblasts and cementoblasts. A PDL single-cell atlas defined cementoblasts and osteoblasts as Plap-1−Ibsp+Sparcl1+ and Plap-1−Ibsp+Col11a2+, respectively. Other populations, such as Nes+ mural cells, S100B+ Schwann cells, and other non-stromal cells, were also identified. RNA velocity analysis suggested that a Plap-1highLy6a+ cell population was the source of PDLCs. Lineage tracing of Plap-1+ PDLCs during periodontal injury showed periodontal tissue regeneration by PDLCs. Our study defines diverse cell populations in PDL and clarifies the role of PDLCs in periodontal tissue homeostasis and repair.

Loss of β‐catenin causes cementum hypoplasia by hampering cementogenic differentiation of Axin2‐expressing cells

“…However, it is still unclear which subset population of Axin2 + progenitor cells differentiate into cementoblasts. Recently, a PDL single‐cell atlas revealed that the stromal compartment was collectively divided into Plap‐1 + fibroblastic cells or Ibsp + osteo‐/cementoblastic cells in a mutually exclusive manner 37 . This finding indicated that Axin2 + cells may also be divided into different subsets with distinct cell fates, which remains further investigation.…”

Efficient Escorting Strategy for Aggregation-Prone Notch EGF Repeats with Sparcl1

“…Approximately 1 mg of mSparcl1-His 6 was recovered from 60 mL of the culture medium. Sparcl1 (SPARC-like 1) is a type I secretory protein (650 amino acids) with three potential N -glycosylation sites and has been implicated as a tumor suppressor protein [ 14 , 15 , 16 , 17 ]. The protein was initially reported to be specific for blood endothelial cells, but recent single-cell RNA sequencing (scRNA-seq) data in periodontal tissues revealed that it is a distinct cementoblast/cementocyte-specific marker [ 14 , 15 ].…”

Unraveling the hidden complexity: Exploring dental tissues through single-cell transcriptional profiling

“…Iwayama et al. revealed the fate of Plap1 + populations with cellular dynamics of the PDL through scRNA-seq in mice [ 52 ]. They first confirmed that Plap1 was a specific marker of the PDL fibroblast lineage (periodontal ligament cells including stem/progenitor cells: PDLCs).…”