title: PIWI-interacting RNA (piRNA) signatures in human cardiac progenitor cells.
abstract: Cardiac progenitors, such as cardiospheres and cardiosphere-derived cells, represent an attractive cell source for cardiac regeneration. The PIWI-interacting RNAs, piRNAs, are an intriguing class of small non-coding RNAs, implicated in the regulation of epigenetic state, maintenance of genomic integrity and stem cell functions. Although non-coding RNAs are an exploiting field in cardiovascular research, the piRNA signatures of cardiac progenitors has not been evaluated yet.We profiled, through microarrays, 15,311 piRNAs expressed in cardiospheres, cardiosphere-derived cells and cardiac fibroblasts. Results showed a set of differentially expressed piRNAs (fold change ≥2, p<0.01): 641 piRNAs were upregulated and 1,301 downregulated in the cardiospheres compared to cardiosphere-derived cells, while 255 and 708 piRNAs resulted up- and down-regulated, respectively, if compared to cardiac fibroblasts. We also identified 181 piRNAs that are overexpressed and 129 are downregulated in cardiosphere-derived cells respect to cardiac fibroblasts.Bioinformatics analysis showed that the deregulated piRNAs were mainly distributed on few chromosomes, suggesting that piRNAs are organized in discrete genomic clusters.Furthermore, the bioinformatics search showed that the most upregulated piRNAs target transposons, especially belonged to LINE-1 class, as validated by qRT-PCR. This reduction is also associated to an activation of AKT signaling, which is beneficial for cardiac regeneration.The present study is the first to show a highly consistent piRNA expression pattern for human cardiac progenitors, likely responsible of their different regenerative power. Moreover, this piRNome analysis may provide new methods for characterize cardiac progenitors and may shed new light on the understanding the complex molecular mechanisms of cardiac regeneration.
authors.affiliation: Fondazione Ri.MED, Palermo, Italy; Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy. Electronic address: sevella@ismett.edu.
authors.forename: Serena
authors.initials: S
authors.lastname: Vella
authors.affiliation: Fondazione Ri.MED, Palermo, Italy; Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lo Nigro
authors.affiliation: Fondazione Ri.MED, Palermo, Italy; Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Galvagno
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Raffa
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Pilato
authors.affiliation: Fondazione Ri.MED, Palermo, Italy; Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Pier Giulio
authors.initials: PG
authors.lastname: Conaldi
mesh_terms: D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering
keywords: Cardiac progenitor cells; Cardiosphere-derived cells; Cardiospheres; piRNA