Biology subjects

D'Ambrosio, C.

Publications and source records attributed to D'Ambrosio, C..

2 recordsLinked to original sources

bioRxiv2024

The RNA binding protein LIN28A mediates chromatin dynamics during neuronal differentiation

The transition of embryonic stem cells (ESCs) from pluripotency to lineage commitment is regulated by multiple mechanisms, including chromatin dynamics and both transcriptional and post-transcriptional processes. Recent advances have highlighted that these mechanisms often interact, forming intricate multi-layered regulatory networks that require detailed characterization. In this study, we demonstrate that the RNA-binding protein LIN28A plays a pivotal role in neuronal differentiation by mediating RNA-dependent interactions with the Polycomb repressive complex 2 (PRC2). This interaction facilitates the eviction of PRC2 from chromatin, thereby activating a neuronal lineage-specific transcriptional program. Proteomic analyses revealed that the LIN28A interactome undergoes substantial remodeling during differentiation, corresponding to changes in LIN28A localization. In ESCs, LIN28A is predominantly nuclear and interacts with several components of the PRC2 complex in an RNA-dependent manner, assisting in chromatin dynamics. Our findings show that in the absence of LIN28A, PRC2 remains associated with chromatin, impairing the expression of genes critical for neuronal differentiation in ESCs. Chromatin immunoprecipitation sequencing (ChIP-seq) further confirmed that loss of LIN28A results in preferential PRC2 occupancy at the promoters of differentiation-associated genes. This study uncovers a novel role for LIN28A in epigenetic remodeling, which is essential for the proper differentiation of ESCs into the neuronal lineage.

molecular biology↗

bioRxiv2020

Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue

Low-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.

physiology↗