Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

Tao Zhang; Pan Wang; Yanxia Liu; Jiankang Zhou; Zhenqing Shi; Kang Cheng; Tuanjie Huang; Xinxin Wang; Greta Luyuan Yang; Bo Yang; Shanshan Ma; Fangxia Guan

doi:10.1007/s00441-018-2815-0

Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

Tao Zhang, Pan Wang, Yanxia Liu, Jiankang Zhou, Zhenqing Shi, Kang Cheng, Tuanjie Huang, Xinxin Wang, Greta Luyuan Yang, Bo Yang, Shanshan Ma, Fangxia Guan

Medicine

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer’s disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer’s disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.

Original language	English (US)
Pages (from-to)	379-393
Number of pages	15
Journal	Cell and Tissue Research
Volume	373
Issue number	2
DOIs	https://doi.org/10.1007/s00441-018-2815-0
State	Published - Aug 1 2018

Keywords

Anti-senescence
FOXQ1
Human umbilical cord mesenchymal stem cells
Migration
Overexpression

ASJC Scopus subject areas

Pathology and Forensic Medicine
Histology
Cell Biology

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Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo. / Zhang, Tao; Wang, Pan; Liu, Yanxia; Zhou, Jiankang; Shi, Zhenqing; Cheng, Kang; Huang, Tuanjie; Wang, Xinxin; Yang, Greta Luyuan; Yang, Bo; Ma, Shanshan; Guan, Fangxia.

In: Cell and Tissue Research, Vol. 373, No. 2, 01.08.2018, p. 379-393.

Research output: Contribution to journal › Article › peer-review

Zhang, Tao ; Wang, Pan ; Liu, Yanxia ; Zhou, Jiankang ; Shi, Zhenqing ; Cheng, Kang ; Huang, Tuanjie ; Wang, Xinxin ; Yang, Greta Luyuan ; Yang, Bo ; Ma, Shanshan ; Guan, Fangxia. / Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo. In: Cell and Tissue Research. 2018 ; Vol. 373, No. 2. pp. 379-393.

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title = "Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo",

abstract = "Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer{\textquoteright}s disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer{\textquoteright}s disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.",

keywords = "Anti-senescence, FOXQ1, Human umbilical cord mesenchymal stem cells, Migration, Overexpression",

author = "Tao Zhang and Pan Wang and Yanxia Liu and Jiankang Zhou and Zhenqing Shi and Kang Cheng and Tuanjie Huang and Xinxin Wang and Yang, {Greta Luyuan} and Bo Yang and Shanshan Ma and Fangxia Guan",

note = "Funding Information: All plasmids (Framework plasmid pHBLV-puro and packaging plasmids psPAX2, pMD2.G) were gifts from the Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology Professor Tanjun Tong. This work was supported by the Natural Science Foundation of China (NSFC 81471306 and 81501200), China Postdoctoral Science Foundation (2015M572122), Innovative Research Team in Science and Technology of the University of Henan Province (15IRTSTHN022), the Plan for Scientific Innovation Talent of Henan Province (154200510008), the Key Research Project of Higher Education of Henan Province (17A310012) and the Research Fund for the Doctoral Program of Higher Education of China (20114101110004). T.Z. and P.W. equally contributed to this work. FX.G. and SS.M. jointly supervised this work. FX.G. is the first corresponding author. Author Disclosure Statement. The authors declare that they have no conflict of interest. Funding Information: This work was supported by the Natural Science Foundation of China (NSFC 81471306 and 81501200), China Postdoctoral Science Foundation (2015M572122), Innovative Research Team in Science and Technology of the University of Henan Province (15IRTSTHN022), the Plan for Scientific Innovation Talent of Henan Province (154200510008), the Key Research Project of Higher Education of Henan Province (17A310012) and the Research Fund for the Doctoral Program of Higher Education of China (20114101110004).",

year = "2018",

month = aug,

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doi = "10.1007/s00441-018-2815-0",

language = "English (US)",

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pages = "379--393",

journal = "Cell and Tissue Research",

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T1 - Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

AU - Zhang, Tao

AU - Wang, Pan

AU - Liu, Yanxia

AU - Zhou, Jiankang

AU - Shi, Zhenqing

AU - Cheng, Kang

AU - Huang, Tuanjie

AU - Wang, Xinxin

AU - Yang, Greta Luyuan

AU - Yang, Bo

AU - Ma, Shanshan

AU - Guan, Fangxia

N1 - Funding Information: All plasmids (Framework plasmid pHBLV-puro and packaging plasmids psPAX2, pMD2.G) were gifts from the Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology Professor Tanjun Tong. This work was supported by the Natural Science Foundation of China (NSFC 81471306 and 81501200), China Postdoctoral Science Foundation (2015M572122), Innovative Research Team in Science and Technology of the University of Henan Province (15IRTSTHN022), the Plan for Scientific Innovation Talent of Henan Province (154200510008), the Key Research Project of Higher Education of Henan Province (17A310012) and the Research Fund for the Doctoral Program of Higher Education of China (20114101110004). T.Z. and P.W. equally contributed to this work. FX.G. and SS.M. jointly supervised this work. FX.G. is the first corresponding author. Author Disclosure Statement. The authors declare that they have no conflict of interest. Funding Information: This work was supported by the Natural Science Foundation of China (NSFC 81471306 and 81501200), China Postdoctoral Science Foundation (2015M572122), Innovative Research Team in Science and Technology of the University of Henan Province (15IRTSTHN022), the Plan for Scientific Innovation Talent of Henan Province (154200510008), the Key Research Project of Higher Education of Henan Province (17A310012) and the Research Fund for the Doctoral Program of Higher Education of China (20114101110004).

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer’s disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer’s disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.

AB - Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer’s disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer’s disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.

KW - Anti-senescence

KW - FOXQ1

KW - Human umbilical cord mesenchymal stem cells

KW - Migration

KW - Overexpression

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