A circular RNA map for human induced pluripotent stem cells of foetal origin

EBioMedicine

Valeria Peli¹  Alessandro Del Gobbo²  Alessandro Cherubini³  Nicola Elvassore⁴  Cristiana Lavazza⁵  Silvia Giovanelli⁶  Lorenza Lazzari⁷  Valentina Bollati⁷  Mario Barilani⁷  Federica Guffanti⁷  Francesca Polveraccio⁷ 

[1] Department of Industrial Engineering, University of Padova, Padova, Italy;Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom;EPIGET Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy;Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy;EPIGET Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy;Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy;Laboratory of Regenerative Medicine – Cell Factory, Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy;

关键词: Cord blood;    Multipotent mesenchymal stromal cells;    hiPSC;    miRNA;    circRNA;    PGRN;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Adult skin fibroblasts represent the most common starting cell type used to generate human induced pluripotent stem cells (F-hiPSC) for clinical studies. Yet, a foetal source would offer unique advantages, primarily the absence of accumulated somatic mutations. Herein, we generated hiPSC from cord blood multipotent mesenchymal stromal cells (MSC-hiPSC) and compared them with F-hiPSC. Assessment of the full activation of the pluripotency gene regulatory network (PGRN) focused on circular RNA (circRNA), recently proposed to participate in the control of pluripotency. Methods: Reprogramming was achieved by a footprint-free strategy. Self-renewal and pluripotency of cord blood MSC-hiPSC were investigated in vitro and in vivo, compared to parental MSC, to embryonic stem cells and to F-hiPSC. High-throughput array-based approaches and bioinformatics analyses were applied to address the PGRN. Findings: Cord blood MSC-hiPSC successfully acquired a complete pluripotent identity. Functional comparison with F-hiPSC showed no differences in terms of i) generation of mesenchymal-like derivatives, ii) their subsequent adipogenic, osteogenic and chondrogenic commitment, and iii) their hematopoietic support ability. At the transcriptional level, specific subsets of mRNA, miRNA and circRNA (n = 4,429) were evidenced, casting a further layer of complexity on the PGRN regulatory crosstalk. Interpretation: A circRNA map of transcripts associated to naïve and primed pluripotency is provided for hiPSC of clinical-grade foetal origin, offering insights on still unreported regulatory circuits of the PGRN to consider for the optimization and development of efficient differentiation protocols for clinical translation. Funding: This research was funded by Ricerca Corrente 2012–2018 by the Italian Ministry of Health.

【 授权许可】

Unknown