Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host
Summary: Stem cell therapy emerges as an effective approach for treating various currently untreatable diseases. However, fatal and unknown risks caused by their systemic use remain to be a major obstacle to clinical application. We developed a functional single-cell RNA sequencing (scRNA-seq) proce...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-08-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422201094X |
| _version_ | 1811310366857101312 |
|---|---|
| author | Kaijing Yan Jinlai Zhang Wen Yin Jeffrey N. Harding Fei Ma Di Wu Haibo Deng Pengfei Han Rui Li Hongxu Peng Xin Song Y. James Kang |
| author_facet | Kaijing Yan Jinlai Zhang Wen Yin Jeffrey N. Harding Fei Ma Di Wu Haibo Deng Pengfei Han Rui Li Hongxu Peng Xin Song Y. James Kang |
| author_sort | Kaijing Yan |
| collection | DOAJ |
| description | Summary: Stem cell therapy emerges as an effective approach for treating various currently untreatable diseases. However, fatal and unknown risks caused by their systemic use remain to be a major obstacle to clinical application. We developed a functional single-cell RNA sequencing (scRNA-seq) procedure and identified that transcriptomic heterogeneity of adipose-derived stromal cells (ADSCs) in cultures is responsible for a fatal embolic risk of these cells in the host. The pro-embolic subpopulation of ADSCs in cultures was sorted by gene set enrichment analysis (GSEA) and verified by a supervised machine learning analysis. A mathematical model was developed and validated for the prediction of embolic risk of cultured ADSCs in animal models and further confirmed by its application to public data. Importantly, modification of culture conditions prevented the embolic risk. This novel procedure can be applied to other aspects of risk assessment and would help further the development of stem cell clinical applications. |
| first_indexed | 2024-04-13T09:57:42Z |
| format | Article |
| id | doaj.art-9376d3b147074d0ca7169c7a81c4d4ca |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T09:57:42Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-9376d3b147074d0ca7169c7a81c4d4ca2022-12-22T02:51:19ZengElsevieriScience2589-00422022-08-01258104822Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the hostKaijing Yan0Jinlai Zhang1Wen Yin2Jeffrey N. Harding3Fei Ma4Di Wu5Haibo Deng6Pengfei Han7Rui Li8Hongxu Peng9Xin Song10Y. James Kang11Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610044, China; Stem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaRegenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610044, ChinaRegenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610044, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaRegenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610044, ChinaStem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, ChinaRegenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610044, China; Stem Cell Biology Laboratory, Tasly Pharmaceutical Co. Ltd, Tianjin 300410, China; Corresponding authorSummary: Stem cell therapy emerges as an effective approach for treating various currently untreatable diseases. However, fatal and unknown risks caused by their systemic use remain to be a major obstacle to clinical application. We developed a functional single-cell RNA sequencing (scRNA-seq) procedure and identified that transcriptomic heterogeneity of adipose-derived stromal cells (ADSCs) in cultures is responsible for a fatal embolic risk of these cells in the host. The pro-embolic subpopulation of ADSCs in cultures was sorted by gene set enrichment analysis (GSEA) and verified by a supervised machine learning analysis. A mathematical model was developed and validated for the prediction of embolic risk of cultured ADSCs in animal models and further confirmed by its application to public data. Importantly, modification of culture conditions prevented the embolic risk. This novel procedure can be applied to other aspects of risk assessment and would help further the development of stem cell clinical applications.http://www.sciencedirect.com/science/article/pii/S258900422201094XStem cells researchcomputational bioinformaticstranscriptomics |
| spellingShingle | Kaijing Yan Jinlai Zhang Wen Yin Jeffrey N. Harding Fei Ma Di Wu Haibo Deng Pengfei Han Rui Li Hongxu Peng Xin Song Y. James Kang Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host iScience Stem cells research computational bioinformatics transcriptomics |
| title | Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host |
| title_full | Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host |
| title_fullStr | Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host |
| title_full_unstemmed | Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host |
| title_short | Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host |
| title_sort | transcriptomic heterogeneity of cultured adscs corresponds to embolic risk in the host |
| topic | Stem cells research computational bioinformatics transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S258900422201094X |
| work_keys_str_mv | AT kaijingyan transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT jinlaizhang transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT wenyin transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT jeffreynharding transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT feima transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT diwu transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT haibodeng transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT pengfeihan transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT ruili transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT hongxupeng transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT xinsong transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost AT yjameskang transcriptomicheterogeneityofculturedadscscorrespondstoembolicriskinthehost |