Open AccessPB1988 CANCER‐ASSOCIATED MECHANISMS OF MESENCHYMAL STEM CELLS REVEALED BY SINGLE‐CELL TRANSCRIPTOME ANALYSIS
Author(s) -
Stucky A.,
Chen X.,
Li C.,
cai J.,
Zhang X.,
Zhong J.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000566444.50697.82
Subject(s) - mesenchymal stem cell , yap1 , cancer research , cancer stem cell , transcriptome , biology , stem cell , cancer , population , medicine , microbiology and biotechnology , gene expression , gene , genetics , transcription factor , environmental health
Background: The detrimental effects of mesenchymal stem cells (MSCs) in some reports eclipse their benefits in clinical application, despite the support and adoption in bone marrow transplantation (BMT). Tumorigenicity has been observed and reported in experimental MSC therapies without clear explanation. Aims: Here we report a subpopulation of MSCs, which are resisted to oste single‐cell transcriptome analysis of individual MSCs at various stages of osteocyte differentiation and gene expression profiles in three discrete stages of osteogenesis. Methods: We identified a subpopulation of osteogenesis‐resistant MSCs which have cancer stem cell chatcteristics. Further pathway analysis indicated that the YAP1, β‐Catenin and Cadherin4/6 pathway involved in osteogenesis‐resistance.. Clinical surveys using 51 clinical databases across 6,965 patients revealed a correlation between YAP1/ β‐Catenin/Cadherin4/6 overexpression and cancer progression. Results: This study suggested that a differentiation‐resistant population of MSC is repsoible for the tumorogenicity of MSC, and intervention of the YAP1, β‐Catenin and Cadherin4/6 pathway could potentially prevent tumorgenicity in MSC therapies. suggests that there is a pre‐exist subpopulation of MSCs with cancer stem cell characteristics. Summary/Conclusion: Those OR‐MSC associated with active YAP1‐Cadherin pathway. Biologically active molecules targeting YAP1/ β‐Catenin/Cadherin could improve MSC therapy for a defined subset of patients by minimize the tumorgenicity of MSCs.