Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques
Abstract
:1. Introduction
2. Experimental Section
2.1. Cells Sources
2.2. Induced Pluripotent Stem Cell (iPS) Line Maintenance
2.3. CD34+ Cell Enrichment
2.4. Real-Time Quantitative (RQ)-PCR Analysis by Low-Density Array/Microfluidic Card
2.5. Immunofluorescence Staining
2.6. Sparse Multivariate Analysis
2.7. Performance Metrics
2.8. Network Inference and Identification of Gene Function
3. Results
3.1. Gene Expression Analysis
3.1.1. CD34+ Cells after UCBT Express Genes of Self-Renewal, Stem Cell Maintenance, and Reprogramming
3.1.2. Self-Renewal, Stem Cell Maintenance, and Reprogramming Genes Are not Differentially Expressed in CD34+ Cells from UCB vs. Adult CD34+ Cells
3.1.3. Genes Regulating Self-Renewal, Cell Reprogramming, and Stem Cell Maintenance Are Overexpressed in CD34+ Cells after UCBT but not after Adult HSCT
3.1.4. Some Reprogramming Genes Are Similarly Expressed in CD34+ Cells after UCBT and iPS Although Their Overall Picture of Gene Expression Is Divergent
3.2. The Transcription of the Overexpressed Genes Is Confirmed by Protein Analysis
3.3. Sparse Multivariate Regularization Analysis
3.3.1. Only Six Genes Are Sufficient to Discriminate UCB from Adult
3.3.2. The Set of the Expression Differences of Fifty-Two Genes Discriminates Cord Blood CD34+ Cells before and after Transplantation
3.3.3. The Set of the Expression Differences of Sixty-Two Genes Discriminates Adult CD34+ Cells before and after Transplantation
3.3.4. After Transplantation Adult Versus Cord Blood CD34+ Cells Acquire a Divergent Transcriptional Asset; Reprogramming Genes Are a Relevant Part of Such Difference
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Cilloni, D.; Petiti, J.; Campia, V.; Podestà, M.; Squillario, M.; Montserrat, N.; Bertaina, A.; Sabatini, F.; Carturan, S.; Berger, M.; et al. Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques. J. Clin. Med. 2020, 9, 1670. https://doi.org/10.3390/jcm9061670
Cilloni D, Petiti J, Campia V, Podestà M, Squillario M, Montserrat N, Bertaina A, Sabatini F, Carturan S, Berger M, et al. Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques. Journal of Clinical Medicine. 2020; 9(6):1670. https://doi.org/10.3390/jcm9061670
Chicago/Turabian StyleCilloni, Daniela, Jessica Petiti, Valentina Campia, Marina Podestà, Margherita Squillario, Nuria Montserrat, Alice Bertaina, Federica Sabatini, Sonia Carturan, Massimo Berger, and et al. 2020. "Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques" Journal of Clinical Medicine 9, no. 6: 1670. https://doi.org/10.3390/jcm9061670