CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis
Abstract Background White adipose tissue includes subcutaneous and visceral adipose tissue (SAT and VAT) with different metabolic features. SAT protects from metabolic disorders, while VAT promotes them. The proliferative and adipogenic potentials of adipose-derived stem cells (ADSCs) are critical f...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-11-01
|
Series: | Stem Cell Research & Therapy |
Subjects: | |
Online Access: | https://doi.org/10.1186/s13287-019-1459-7 |
id |
doaj-efc94d56453341f19d1a405f18f85571 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhenzhen Pan Zixin Zhou Huiying Zhang Hui Zhao Peixuan Song Di Wang Jilong Yin Wanyi Zhao Zhaoxiang Xie Fuwu Wang Yan Li Chun Guo Faliang Zhu Lining Zhang Qun Wang |
spellingShingle |
Zhenzhen Pan Zixin Zhou Huiying Zhang Hui Zhao Peixuan Song Di Wang Jilong Yin Wanyi Zhao Zhaoxiang Xie Fuwu Wang Yan Li Chun Guo Faliang Zhu Lining Zhang Qun Wang CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis Stem Cell Research & Therapy CD90 Adipose-derived stem cell Proliferation Mitotic clonal expansion Adipose tissue Metabolic homeostasis |
author_facet |
Zhenzhen Pan Zixin Zhou Huiying Zhang Hui Zhao Peixuan Song Di Wang Jilong Yin Wanyi Zhao Zhaoxiang Xie Fuwu Wang Yan Li Chun Guo Faliang Zhu Lining Zhang Qun Wang |
author_sort |
Zhenzhen Pan |
title |
CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis |
title_short |
CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis |
title_full |
CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis |
title_fullStr |
CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis |
title_full_unstemmed |
CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis |
title_sort |
cd90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating akt activation that influences adipose tissue and metabolic homeostasis |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2019-11-01 |
description |
Abstract Background White adipose tissue includes subcutaneous and visceral adipose tissue (SAT and VAT) with different metabolic features. SAT protects from metabolic disorders, while VAT promotes them. The proliferative and adipogenic potentials of adipose-derived stem cells (ADSCs) are critical for maintaining adipose tissue homeostasis through driving adipocyte hyperplasia and inhibiting pathological hypertrophy. However, it remains to be elucidated the critical molecules that regulate different potentials of subcutaneous and visceral ADSCs (S-ADSCs, V-ADSCs) and mediate distinct metabolic properties of SAT and VAT. CD90 is a glycosylphosphatidylinositol-anchored protein on various cells, which is also expressed on ADSCs. However, its expression patterns and differential regulation on S-ADSCs and V-ADSCs remain unclear. Methods S-ADSCs and V-ADSCs were detected for CD90 expression. Proliferation, colony formation, cell cycle, mitotic clonal expansion, and adipogenic differentiation were assayed in S-ADSCs, V-ADSCs, or CD90-silenced S-ADSCs. Glucose tolerance test and adipocyte hypertrophy were examined in mice after silencing of CD90 in SAT. CD90 expression and its association with CyclinD1 and Leptin were analyzed in adipose tissue from mice and humans. Regulation of AKT by CD90 was detected using a co-transfection system. Results Compared with V-ADSCs, S-ADSCs expressed high level of CD90 and showed increases in proliferation, mitotic clonal expansion, and adipogenic differentiation, together with AKT activation and G1-S phase transition. CD90 silencing inhibited AKT activation and S phase entry, thereby curbing proliferation and mitotic clonal expansion of S-ADSCs. In vivo CD90 silencing in SAT inhibited S-ADSC proliferation, which caused adipocyte hypertrophy and glucose intolerance in mice. Furthermore, CD90 was highly expressed in SAT rather than in VAT in human and mouse, which had positive correlation with CyclinD1 but negative correlation with Leptin. CD90 promoted AKT activation through recruiting its pleckstrin homology domain to plasma membrane. Conclusions CD90 is differentially expressed on S-ADSCs and V-ADSCs, and plays critical roles in ADSC proliferation, mitotic clonal expansion, and hemostasis of adipose tissue and metabolism. These findings identify CD90 as a crucial modulator of S-ADSCs and V-ADSCs to mediate distinct metabolic features of SAT and VAT, thus proposing CD90 as a valuable biomarker or target for evaluating ADSC potentials, monitoring or treating obesity-associated metabolic disorders. |
topic |
CD90 Adipose-derived stem cell Proliferation Mitotic clonal expansion Adipose tissue Metabolic homeostasis |
url |
https://doi.org/10.1186/s13287-019-1459-7 |
work_keys_str_mv |
AT zhenzhenpan cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT zixinzhou cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT huiyingzhang cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT huizhao cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT peixuansong cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT diwang cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT jilongyin cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT wanyizhao cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT zhaoxiangxie cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT fuwuwang cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT yanli cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT chunguo cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT faliangzhu cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT liningzhang cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis AT qunwang cd90servesasdifferentialmodulatorofsubcutaneousandvisceraladiposederivedstemcellsbyregulatingaktactivationthatinfluencesadiposetissueandmetabolichomeostasis |
_version_ |
1724412344236244992 |
spelling |
doaj-efc94d56453341f19d1a405f18f855712020-11-29T12:04:51ZengBMCStem Cell Research & Therapy1757-65122019-11-0110111810.1186/s13287-019-1459-7CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasisZhenzhen Pan0Zixin Zhou1Huiying Zhang2Hui Zhao3Peixuan Song4Di Wang5Jilong Yin6Wanyi Zhao7Zhaoxiang Xie8Fuwu Wang9Yan Li10Chun Guo11Faliang Zhu12Lining Zhang13Qun Wang14Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversitySchool of Mathematics and Statistics, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Science, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Science, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong UniversityAbstract Background White adipose tissue includes subcutaneous and visceral adipose tissue (SAT and VAT) with different metabolic features. SAT protects from metabolic disorders, while VAT promotes them. The proliferative and adipogenic potentials of adipose-derived stem cells (ADSCs) are critical for maintaining adipose tissue homeostasis through driving adipocyte hyperplasia and inhibiting pathological hypertrophy. However, it remains to be elucidated the critical molecules that regulate different potentials of subcutaneous and visceral ADSCs (S-ADSCs, V-ADSCs) and mediate distinct metabolic properties of SAT and VAT. CD90 is a glycosylphosphatidylinositol-anchored protein on various cells, which is also expressed on ADSCs. However, its expression patterns and differential regulation on S-ADSCs and V-ADSCs remain unclear. Methods S-ADSCs and V-ADSCs were detected for CD90 expression. Proliferation, colony formation, cell cycle, mitotic clonal expansion, and adipogenic differentiation were assayed in S-ADSCs, V-ADSCs, or CD90-silenced S-ADSCs. Glucose tolerance test and adipocyte hypertrophy were examined in mice after silencing of CD90 in SAT. CD90 expression and its association with CyclinD1 and Leptin were analyzed in adipose tissue from mice and humans. Regulation of AKT by CD90 was detected using a co-transfection system. Results Compared with V-ADSCs, S-ADSCs expressed high level of CD90 and showed increases in proliferation, mitotic clonal expansion, and adipogenic differentiation, together with AKT activation and G1-S phase transition. CD90 silencing inhibited AKT activation and S phase entry, thereby curbing proliferation and mitotic clonal expansion of S-ADSCs. In vivo CD90 silencing in SAT inhibited S-ADSC proliferation, which caused adipocyte hypertrophy and glucose intolerance in mice. Furthermore, CD90 was highly expressed in SAT rather than in VAT in human and mouse, which had positive correlation with CyclinD1 but negative correlation with Leptin. CD90 promoted AKT activation through recruiting its pleckstrin homology domain to plasma membrane. Conclusions CD90 is differentially expressed on S-ADSCs and V-ADSCs, and plays critical roles in ADSC proliferation, mitotic clonal expansion, and hemostasis of adipose tissue and metabolism. These findings identify CD90 as a crucial modulator of S-ADSCs and V-ADSCs to mediate distinct metabolic features of SAT and VAT, thus proposing CD90 as a valuable biomarker or target for evaluating ADSC potentials, monitoring or treating obesity-associated metabolic disorders.https://doi.org/10.1186/s13287-019-1459-7CD90Adipose-derived stem cellProliferationMitotic clonal expansionAdipose tissueMetabolic homeostasis |