A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway

Abstract Background SATB2-associated syndrome (SAS) is a multisystem disorder caused by mutation of human SATB2 gene. Tooth agenesis is one of the most common phenotypes observed in SAS. Our study aimed at identifying novel variant of SATB2 in a patient with SAS, and to investigate the cellular and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tianyi Xin, Qian Li, Rushui Bai, Ting Zhang, Yanheng Zhou, Yuehua Zhang, Bing Han, Ruili Yang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	SATB2 Tooth agenesis Odontogenesis Dental pulp stem cells Wnt/β-catenin signaling Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/e29a3f12811a412799274e14e498f664
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e29a3f12811a412799274e14e498f664
record_format	dspace
spelling	oai:doaj.org-article:e29a3f12811a412799274e14e498f6642021-12-05T12:05:43ZA novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway10.1186/s13287-021-02660-81757-6512https://doaj.org/article/e29a3f12811a412799274e14e498f6642021-12-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02660-8https://doaj.org/toc/1757-6512Abstract Background SATB2-associated syndrome (SAS) is a multisystem disorder caused by mutation of human SATB2 gene. Tooth agenesis is one of the most common phenotypes observed in SAS. Our study aimed at identifying novel variant of SATB2 in a patient with SAS, and to investigate the cellular and molecular mechanism of tooth agenesis caused by SATB2 mutation. Methods We applied whole exome sequencing (WES) to identify the novel mutation of SATB2 in a Chinese patient with SAS. Construction and overexpression of wild-type and the mutant vector was performed, followed by functional analysis including flow cytometry assay, fluorescent immunocytochemistry, western blot, quantitative real-time PCR and Alizarin Red S staining to investigate its impact on hDPSCs and the underlying mechanisms. Results As a result, we identified a novel frameshift mutation of SATB2 (c. 376_378delinsTT) in a patient with SAS exhibiting tooth agenesis. Human DPSCs transfected with mutant SATB2 showed decreased cell proliferation and odontogenic differentiation capacity compared with hDPSCs transfected with wild-type SATB2 plasmid. Mechanistically, mutant SATB2 failed to translocate into nucleus and distributed in the cytoplasm, failing to activate Wnt/β-catenin signaling pathway, whereas the wild-type SATB2 translocated into the nucleus and upregulated the expression of active β-catenin. When we used Wnt inhibitor XAV939 to treat hDPSCs transfected with wild-type SATB2 plasmid, the increased odontogenic differentiation capacity was attenuated. Furthermore, we found that SATB2 mutation resulted in the upregulation of DKK1 and histone demethylase JHDM1D to inhibit Wnt/β-catenin signaling pathway. Conclusion We identified a novel frameshift mutation of SATB2 (c.376_378delinsTT, p.Leu126SerfsX6) in a Chinese patient with SATB2-associated syndrome (SAS) exhibiting tooth agenesis. Mechanistically, SATB2 regulated osteo/odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway by regulating DKK1 and histone demethylase JHDM1D.Tianyi XinQian LiRushui BaiTing ZhangYanheng ZhouYuehua ZhangBing HanRuili YangBMCarticleSATB2Tooth agenesisOdontogenesisDental pulp stem cellsWnt/β-catenin signalingMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SATB2 Tooth agenesis Odontogenesis Dental pulp stem cells Wnt/β-catenin signaling Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	SATB2 Tooth agenesis Odontogenesis Dental pulp stem cells Wnt/β-catenin signaling Medicine (General) R5-920 Biochemistry QD415-436 Tianyi Xin Qian Li Rushui Bai Ting Zhang Yanheng Zhou Yuehua Zhang Bing Han Ruili Yang A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
description	Abstract Background SATB2-associated syndrome (SAS) is a multisystem disorder caused by mutation of human SATB2 gene. Tooth agenesis is one of the most common phenotypes observed in SAS. Our study aimed at identifying novel variant of SATB2 in a patient with SAS, and to investigate the cellular and molecular mechanism of tooth agenesis caused by SATB2 mutation. Methods We applied whole exome sequencing (WES) to identify the novel mutation of SATB2 in a Chinese patient with SAS. Construction and overexpression of wild-type and the mutant vector was performed, followed by functional analysis including flow cytometry assay, fluorescent immunocytochemistry, western blot, quantitative real-time PCR and Alizarin Red S staining to investigate its impact on hDPSCs and the underlying mechanisms. Results As a result, we identified a novel frameshift mutation of SATB2 (c. 376_378delinsTT) in a patient with SAS exhibiting tooth agenesis. Human DPSCs transfected with mutant SATB2 showed decreased cell proliferation and odontogenic differentiation capacity compared with hDPSCs transfected with wild-type SATB2 plasmid. Mechanistically, mutant SATB2 failed to translocate into nucleus and distributed in the cytoplasm, failing to activate Wnt/β-catenin signaling pathway, whereas the wild-type SATB2 translocated into the nucleus and upregulated the expression of active β-catenin. When we used Wnt inhibitor XAV939 to treat hDPSCs transfected with wild-type SATB2 plasmid, the increased odontogenic differentiation capacity was attenuated. Furthermore, we found that SATB2 mutation resulted in the upregulation of DKK1 and histone demethylase JHDM1D to inhibit Wnt/β-catenin signaling pathway. Conclusion We identified a novel frameshift mutation of SATB2 (c.376_378delinsTT, p.Leu126SerfsX6) in a Chinese patient with SATB2-associated syndrome (SAS) exhibiting tooth agenesis. Mechanistically, SATB2 regulated osteo/odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway by regulating DKK1 and histone demethylase JHDM1D.
format	article
author	Tianyi Xin Qian Li Rushui Bai Ting Zhang Yanheng Zhou Yuehua Zhang Bing Han Ruili Yang
author_facet	Tianyi Xin Qian Li Rushui Bai Ting Zhang Yanheng Zhou Yuehua Zhang Bing Han Ruili Yang
author_sort	Tianyi Xin
title	A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
title_short	A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
title_full	A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
title_fullStr	A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
title_full_unstemmed	A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
title_sort	novel mutation of satb2 inhibits odontogenesis of human dental pulp stem cells through wnt/β-catenin signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e29a3f12811a412799274e14e498f664
work_keys_str_mv	AT tianyixin anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT qianli anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT rushuibai anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT tingzhang anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT yanhengzhou anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT yuehuazhang anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT binghan anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT ruiliyang anovelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT tianyixin novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT qianli novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT rushuibai novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT tingzhang novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT yanhengzhou novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT yuehuazhang novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT binghan novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway AT ruiliyang novelmutationofsatb2inhibitsodontogenesisofhumandentalpulpstemcellsthroughwntbcateninsignalingpathway
_version_	1718372286104338432

A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway

Ejemplares similares