Biology subjects

Piacentini, L.

Publications and source records attributed to Piacentini, L..

4 recordsLinked to original sources

bioRxiv2023

Deciphering abdominal aortic diseases through T-cell clonal repertoire of perivascular adipose tissue

Recent studies suggested that immune-mediated inflammation of perivascular adipose tissue (PVAT) of abdominal aortic aneurysms (AAA) contributes to disease development and progression. Whether the PVAT of AAA is characterized by a specific adaptive immune signature remains unknown. To investigate this hypothesis, we sequenced the T-cell receptor {beta}-chain (TCR{beta}) in the PVAT of AAA patients and compared with patients with aortic occlusive disease (AOD), who share with the former anatomical site of the lesion, risk factors but differ in pathogenic mechanisms. Our results demonstrate that AAA patients have a lower repertoire diversity than those with AOD and significant differences in V/J gene segment usage. Furthermore, we identified a set of 7 public TCR{beta} clonotypes that distinguished AAA and AOD with very high accuracy. We also found that the TCR{beta} repertoire differentially characterizes small and large AAA (aortic diameter <55 mm and [≥]55 mm, respectively). This work supports the hypothesis that T-cell-mediated immunity is fundamental in AAA pathogenesis and opens up new clinical perspectives. SummaryDifferent immune mechanisms may play a key role in the pathogenesis of distal aortic aneurysm and aortoiliac occlusive disease. The TCR{beta} repertoire of perivascular adipose tissue differs between the two pathologic conditions, suggesting the involvement of specific antigen-specific immune responses.

immunology↗

bioRxiv2020

Transposable Element activation promotes neurodegeneration in a Drosophila model of Huntington's disease

Huntingtons disease (HD) is a late-onset, autosomal dominant disorder characterized by progressive motor dysfunction, cognitive decline and psychiatric disturbances. The most prominent pathological manifestation is a selective loss of medium-sized spiny neurons of the striatum. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a stretch of polyglutamine at the amino-terminal of the HD protein, Huntingtin (Htt). Despite the accumulation of an impressive amount of data on the molecular basis of neurodegeneration, no therapeutic treatments are available and new pharmacological targets are needed. Transposable Elements (TEs) are mobile genetic elements that constitute a large fraction of eukaryotic genomes. Retrotransposons (RTEs) replicate through an RNA intermediate and represent approximately 40% and 30% of the human and Drosophila genomes. Mounting evidence suggests that mammalian RTEs are normally active during neurogenesis and may be involved in diseases of the nervous system. Here we show that TE expression and mobilization are increased in a Drosophila melanogaster HD model. By inhibiting TE mobilization with Reverse Transcriptase inhibitors, polyQ-dependent eye neurodegeneration and genome instability in larval brains are rescued and fly lifespan is increased. These results suggest that TE activation may be involved in polyQ-induced neurotoxicity and a potential pharmacological target.

neuroscience↗

bioRxiv2018

Heterochromatin protein 1 (HP1) is intrinsically required for post-transcriptional regulation of Drosophila Germline Stem Cell (GSC) maintenance

A very important open question in stem cells regulation is how the fine balance between GSCs self-renewal and differentiation is orchestrated at the molecular level. In the past several years much progress has been made in understanding the molecular mechanisms underlying intrinsic and extrinsic controls of GSC regulation but the complex gene regulatory networks that regulate stem cell behavior are only partially understood. HP1 is a dynamic epigenetic determinant mainly involved in heterochromatin formation, epigenetic gene silencing and telomere maintenance. Furthermore, recent studies have revealed the importance of HP1 in DNA repair, sister chromatid cohesion and, surprisingly, in positive regulation of gene expression. Here, we show that HP1 plays a crucial role in the control of GSC homeostasis in Drosophila. Our findings demonstrate that HP1 is required intrinsically to promote GSC self-renewal and progeny differentiation by directly stabilizing the transcripts of key genes involved in GSCs maintenance.

genetics↗

bioRxiv2018

Survival protection mechanisms and genetic variability induction after stress: two sides of the same Hsp70 coin

Previous studies have shown that heat shock stress may increase transcription levels and, in some cases, also the transposition of certain transposable elements (TEs) in Drosophila and other organisms. Other studies have also demonstrated that heat shock chaperones as Hsp90 and Hop are involved in repressing transposons activity in Drosophila melanogaster by their involvement in crucial steps of the biogenesis of Piwi-interacting RNAs (piRNAs), the largest class of germline-enriched small non-coding RNA implicated in the epigenetic silencing of TEs. However, a satisfying picture of how many chaperones and their respective functional roles could be involved in repressing transposons in germ cell is still unknown. Here we show that in Drosophila heat shock activates transposon's expression at post-transcriptional level by disrupting a repressive chaperone complex by a decisive role of the stress-inducible chaperone Hsp70. We found that stress-induced transposons activation is triggered by an interaction of Hsp70 with the Hsc70-Hsp90 complex and other factors all involved in piRNA biogenesis in both ovaries and testes. Such interaction induces a displacement of all such factors to the lysosomes resulting in a functional collapse of piRNA biogenesis. In support of a significant role of Hsp70 in transposon activation after stress, we found that the expression under normal conditions of Hsp70 in transgenic flies increases the amount of transposon transcripts and displaces the components of chaperon machinery outside the nuage as observed after heat shock. So that, our results demonstrate that heat shock stress is capable to increase the expression of transposons at post-transcriptional level by affecting piRNA biogenesis through the action of the inducible chaperone Hsp70. We think that such mechanism proposes relevant evolutionary implications. In presence of drastic environmental changes, Hsp70 plays a key dual role in increasing both the survival probability of individuals and the genetic variability in their germ cells. This in turn should be translated into an increase of genetic variability inside the populations thus potentiating their evolutionary plasticity and evolvability.

genetics↗