Takahashi Yuji, Yasuhara Rika, Tanaka Junichi, Nakano Haruhisa, Maki Koutaro, Mishima Kenji
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, 142-8555, Japan; Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan.
Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan.
J Oral Biosci. 2023 Mar;65(1):40-46. doi: 10.1016/j.job.2023.01.005. Epub 2023 Jan 21.
Tissue differentiation is regulated by transcription factors. This study aimed to identify candidate transcription factors that induce periodontal ligament (PDL) cell differentiation in human pluripotent stem cells (hPSCs).
Human PDL tissues were scraped from the root surfaces of extracted teeth for orthodontic treatment and cultured using the explant culture method. We used RNA-seq to generate gene expression profiles of third-passage PDL cells and compared them with those of undifferentiated human induced pluripotent stem cells (hiPSCs) and human embryonic stem cell (hESC)-derived neural crest (NC) cells (publicly available data).
Primary cultured PDL cells exhibited a spindle-shaped fibroblast-like appearance and the gene expression of several PDL cell-specific markers. The gene expression profiles of PDL cells were relatively similar to those of hESC-derived NC cells but not those of undifferentiated hiPSCs. Thirty-seven transcription factors were identified as upregulated genes in PDL cells. Pathway analysis showed that differentially expressed genes were enriched in several functional groups and pathways, including the SMAD 2/3 nuclear pathway.
We identified 37 upregulated transcription genes in primary cultured PDL cells compared with hESC-derived NC cells. Regulating these genes and the SMAD signaling pathway may be promising ways to induce PDL cells from hPSC-derived NC cells.
组织分化受转录因子调控。本研究旨在鉴定可诱导人多能干细胞（hPSC）向牙周膜（PDL）细胞分化的候选转录因子。
从正畸治疗拔除牙齿的根面刮取人PDL组织，采用组织块培养法进行培养。我们利用RNA测序生成第三代PDL细胞的基因表达谱，并将其与未分化的人诱导多能干细胞（hiPSC）和人胚胎干细胞（hESC）来源的神经嵴（NC）细胞的基因表达谱进行比较（公开可用数据）。
原代培养的PDL细胞呈现纺锤形的成纤维细胞样外观，并表达几种PDL细胞特异性标志物的基因。PDL细胞的基因表达谱与hESC来源的NC细胞相对相似，但与未分化的hiPSC不同。37种转录因子被鉴定为PDL细胞中的上调基因。通路分析表明，差异表达基因富集于几个功能组和通路中，包括SMAD 2/3核通路。
与hESC来源的NC细胞相比，我们在原代培养的PDL细胞中鉴定出37个上调的转录基因。调控这些基因和SMAD信号通路可能是从hPSC来源的NC细胞诱导产生PDL细胞的有前景的方法。
