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

Barilani, Mario, Cherubini, Alessandro, Peli, Valeria, Polveraccio, Francesca, Bollati, Valentina, Guffanti, Federica, Del Gobbo, Alessandro, Lavazza, Cristiana, Giovanelli, Silvia, Elvassore, Nicola and Lazzari, Lorenza 2020. A circular RNA map for human induced pluripotent stem cells of foetal origin. EBioMedicine 57 , 102848. 10.1016/j.ebiom.2020.102848

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Abstract

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. • View related content for this article 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Publisher:	Elsevier
ISSN:	2352-3964
Date of First Compliant Deposit:	31 August 2021
Date of Acceptance:	4 June 2020
Last Modified:	05 Jun 2023 00:10
URI:	https://orca.cardiff.ac.uk/id/eprint/143757

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