Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques

Daniela Cilloni, Jessica Petiti, Valentina Campia, Marina Podestà, Margherita Squillario, Nuria Montserrat, Alice Bertaina, Federica Sabatini, Sonia Carturan, Massimo Berger, Francesco Saglio, Giuseppe Bandini, Francesca Bonifazi, Franca Fagioli, Lorenzo Moretta, Giuseppe Saglio, Alessandro Verri, Annalisa Barla, Franco Locatelli, Francesco Frassoni

Research output: Contribution to journalArticlepeer-review

Abstract

During the phase of proliferation needed for hematopoietic reconstitution following transplantation, hematopoietic stem/progenitor cells (HSPC) must express genes involved in stem cell self-renewal. We investigated the expression of genes relevant for self-renewal and expansion of HSPC (operationally defined as CD34+ cells) in steady state and after transplantation. Specifically, we evaluated the expression of ninety-one genes that were analyzed by real-time PCR in CD34+ cells isolated from (i) 12 samples from umbilical cord blood (UCB); (ii) 15 samples from bone marrow healthy donors; (iii) 13 samples from bone marrow after umbilical cord blood transplant (UCBT); and (iv) 29 samples from patients after transplantation with adult hematopoietic cells. The results show that transplanted CD34+ cells from adult cells acquire an asset very different from transplanted CD34+ cells from cord blood. Multivariate machine learning analysis (MMLA) showed that four specific gene signatures can be obtained by comparing the four types of CD34+ cells. In several, but not all cases, transplanted HSPC from UCB overexpress reprogramming genes. However, these remarkable changes do not alter the commitment to hematopoietic lineage. Overall, these results reveal undisclosed aspects of transplantation biology.

Original languageEnglish
JournalJournal of Clinical Medicine
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 1 2020

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