Single-Cell Transcriptomic Sequencing Analyses of Cell Heterogeneity During Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells

Qu, Rongmei; He, Kai; Fan, Tao; Yang, Yuchao; Mai, Liyao; Lian, Zhiwei; Zhou, Zhaoxi; Peng, Yan; Khan, Asmat Ullah; Sun, Bing; Huang, Xiaolan; Ouyang, Jun; Pan, Xinghua; Dai, Jingxing; Huang, Wenhua

doi:10.1002/stem.3442

Cited by 12 publications

(4 citation statements)

References 57 publications

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“…The osteogenic differentiation trajectory was found to be regulated by Prostaglandin-Endoperoxide Synthase 1 ( PTGS1 ) [ 43 ], Cell Migration Inducing Hyaluronidase 1 ( CEMIP ) [ 44 ], and Dehydrogenase/Reductase 3 ( DHRS3 ) [ 45 ], which supports our observations that these results were established from early stages. In addition to some genes with known functions, we found that there were significant differences in many unreported genes, such as SERPINE2 [ 46 ], SFRP1 , KRT7 , PI16 , and CPE , which may be potential targets to optimize the efficiency of osteogenic induction [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Combining single-cell transcriptomics and CellTagging to identify differentiation trajectories of human adipose-derived mesenchymal stem cells

et al. 2023

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Background Mesenchymal stromal cells (MSCs) have attracted great attention in the application of cell-based therapy because of their pluripotent differentiation and immunomodulatory ability. Due to the limited number of MSCs isolated from donor tissues, a large number of MSCs need to be expanded in a traditional two-dimensional cell culture device to obtain a sufficient therapeutic amount. However, long-term cultivation of MSCs in vitro has been proven to reduce their differentiation potential and change their immunomodulatory characteristics. We aimed to explore the cellular heterogeneity and differentiation potential of different MSCs expanded in vitro and reconstruct the complex cloning track of cells in the process of differentiation. Methods Single cell transcriptome sequencing was combined with ‘CellTagging’, which is a composite barcode indexing method that can capture the cloning history and cell identity in parallel to track the differentiation process of the same cell over time. Results Through the single-cell transcriptome and CellTagging, we found that the heterogeneity of human adipose tissue derived stem cells (hADSCs) in the early stage of culture was very limited. With the passage, the cells spontaneously differentiated during the process of division and proliferation, and the heterogeneity of the cells increased. By tracing the differentiation track of cells, we found most cells have the potential for multidirectional differentiation, while a few cells have the potential for unidirectional differentiation. One subpopulation of hADSCs with the specific osteoblast differentiation potential was traced from the early stage to the late stage, which indicates that the differentiation trajectories of the cells are determined in the early stages of lineage transformation. Further, considering that all genes related to osteogenic differentiation have not yet been determined, we identified that there are some genes that are highly expressed specifically in the hADSC subsets that can successfully differentiate into osteoblasts, such as Serpin Family E Member 2 (SERPINE2), Secreted Frizzled Related Protein 1 (SFRP1), Keratin 7 (KRT7), Peptidase Inhibitor 16 (PI16), and Carboxypeptidase E (CPE), which may be key regulatory genes for osteogenic induction, and finally proved that the SERPINE2 gene can promote the osteogenic process. Conclusion The results of this study contribute toward the exploration of the heterogeneity of hADSCs and improving our understanding of the influence of heterogeneity on the differentiation potential of cells. Through this study, we found that the SERPINE2 gene plays a decisive role in the osteogenic differentiation of hADSCs, which lays a foundation for establishing a more novel and complete induction system.

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Section: Resultsmentioning

confidence: 99%

Combining single-cell transcriptomics and CellTagging to identify differentiation trajectories of human adipose-derived mesenchymal stem cells

et al. 2023

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“…It remains to be clarified whether the adipogenic cells have the potential to fully differentiate into mature adipocytes, and if so, what the biological functions of adipocytes during bone repair are. Given that recent studies with scRNA-seq analysis revealed heterogeneous cell populations in skeletal tissues in both mice and humans [ 40 , [51] , [52] , [53] , [54] , [55] ], further integrative analysis will provide better understanding of the identified cell populations in terms of the similarity and specificity of the mesenchymal cells in the calvaria and bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing unravels heterogeneity of skeletal progenitors and cell–cell interactions underlying the bone repair process

Nakayama

Okada

Seki

et al. 2022

Regenerative Therapy

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“…Transcriptomic sequencing approaches have been widely used in medical studies, such as constructing the transcriptomic signatures of intestinal failure-associated liver diseases ( 119 ), revealing the pathogenesis of COVID-19 ( 120 ), identifying diagnostic biomarkers and therapeutic targets of multiple meylomas ( 121 ), and deciphering cell heterogeneity during osteogenesis of human adipose-derived mesenchymal stem cells ( 122 ).…”

Section: Technology-based Omicsmentioning

confidence: 99%

Advances and Trends in Omics Technology Development

2022

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The human history has witnessed the rapid development of technologies such as high-throughput sequencing and mass spectrometry that led to the concept of “omics” and methodological advancement in systematically interrogating a cellular system. Yet, the ever-growing types of molecules and regulatory mechanisms being discovered have been persistently transforming our understandings on the cellular machinery. This renders cell omics seemingly, like the universe, expand with no limit and our goal toward the complete harness of the cellular system merely impossible. Therefore, it is imperative to review what has been done and is being done to predict what can be done toward the translation of omics information to disease control with minimal cell perturbation. With a focus on the “four big omics,” i.e., genomics, transcriptomics, proteomics, metabolomics, we delineate hierarchies of these omics together with their epiomics and interactomics, and review technologies developed for interrogation. We predict, among others, redoxomics as an emerging omics layer that views cell decision toward the physiological or pathological state as a fine-tuned redox balance.

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Single-Cell Transcriptomic Sequencing Analyses of Cell Heterogeneity During Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells

Cited by 12 publications

References 57 publications

Combining single-cell transcriptomics and CellTagging to identify differentiation trajectories of human adipose-derived mesenchymal stem cells

Combining single-cell transcriptomics and CellTagging to identify differentiation trajectories of human adipose-derived mesenchymal stem cells

Single-cell RNA sequencing unravels heterogeneity of skeletal progenitors and cell–cell interactions underlying the bone repair process

Advances and Trends in Omics Technology Development

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