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ARTICLE

Single-cell sequencing analysis reveals the molecular mechanism of promotion of SCAP proliferation upon AZD2858 treatment

YIFAN XU^1,#, DONGMEI CHENG^1,#, LEI HU¹, XIN DONG², LIYING LV², CHEN ZHANG², JIAN ZHOU^1,3,4,*

1 Beijing Laboratory of Oral Health, School of Stomatology, Capital Medical University, Beijing, 100050, China
2 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China
3 Department of VIP Dental Service, School of Stomatology, Capital Medical University, Beijing, 100050, China
4 Laboratory for Oral and General Health Integration and Translation, Beijing Tian Tan Hospital, Capital Medical University, Beijing, 100070, China

* Corresponding Author: JIAN ZHOU. Email:
# These authors contributed equally to this article

(This article belongs to the Special Issue: Cell-Based Regenerative Therapies)

BIOCELL 2023, 47(4), 825-836. https://doi.org/10.32604/biocell.2023.026122

Received 17 August 2022; Accepted 28 November 2022; Issue published 08 March 2023

Abstract

The Wnt/β-catenin signaling pathway is the main target of tooth regeneration regulation. Treatment of cells with AZD2858 stimulates the Wnt/β-catenin signaling pathway, yet the function of this pathway in tooth regeneration remains unclear. Here, we found that AZD2858 promotes the accumulation of β-catenin in the nuclei of stem cells from the apical papilla (SCAPs) and enhances cell proliferation. Single-cell sequencing was performed on SCAPs treated with AZD2858. Eight clusters were identified, namely SCAPs-CNTNAP2, SCAPs-DTL, SCAPs-MYH11, SCAPs-MKI67, SCAPs-CXCL8, SCAPs-TPM2, SCAPs-IFIT2 and SCAPs-NEK10. The pseudo-time trajectory analysis showed that AZD2858 enhanced the evolution of SCAPs from SCAPs-TMP2 clusters to SCAPs-MYH11, SCAPs-CNTNAPs and SCAPs-NEK10 clusters via up-regulation of PRKCA, SMURF2, MAGI2, RBMS3, EXT1, CAMK2D, PLCB4, and PLCB1. These results demonstrate that AZD2858 enhances the proliferation of SCAPs-TPM2 cluster by activating the non-canonical Wnt/β-catenin signaling pathway.

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Keywords

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