Biology subjects

Fasciani, A.

Publications and source records attributed to Fasciani, A..

3 recordsLinked to original sources

bioRxiv2026

Human basal radial glia morphotypes are transcriptionally distinct and exhibit different cell fate determination

Basal radial glia (bRG) are key neural progenitors driving human neocortical expansion. They exhibit remarkable morphological heterogeneity, yet the stability and functional significance of their distinct morphotypes remains unclear. Using human cortical brain organoids combined with long-term live imaging and morphology-resolved spatial transcriptomics (CellShape-seq), we show that bRG morphotypes display distinct morphodynamic behaviors, proliferative capacities and transcriptional profiles. While bifurcated bRG remodel extensively during mitosis to produce morphologically diverse progeny, multipolar cells are most morphologically flexible during interphase. Multipolar bRG further show the greatest proliferative capacity and the transcriptional signature related to progenitor state. Bifurcated bRG are least proliferative and are enriched for the multifunctional gene expression regulator YBX1. Pharmacological inhibition of YBX1 depletes bifurcated bRG, reduces neurogenesis, and promotes glial commitment. Our findings link progenitor morphology, gene expression and fate, providing a framework for understanding the cellular logic of human cortical development.

neuroscience↗

bioRxiv2024

ANP32E drives vulnerability to ATR inhibitors by inducing R-loops-dependent Transcription Replication Conflicts in Triple Negative Breast Cancer

Oncogene-induced replicative stress (RS) plays a central role in tumor progression, leading to genomic instability by eliciting transcription replication conflicts (TRCs), which represent the major source of R-loops, that ultimately favors the onset of the DNA damage response (DDR). We investigated the pathogenic contribution of chromatin factors in increasing TRCs and R-loop frequencies in cancer. We found that in breast cancer patients the concomitant upregulation of MYC and the H2A.Z-specific chaperone ANP32E correlated with an increase genome instability. Genome-wide profiling revealed that the ANP32E-dependent increases turnover of H2A.Z altered RNApol II processivity, leading to accumulation of long R-loops at TRCs. We showed that ANP32E upregulation increases TRCs and activates an ATR-dependent DDR, which predispose cancer cells to R-loop-mediated genomic fragility. By exploiting the vulnerability of ANP32E-expressing cancer cells to ATR inhibitors, we found that tumors relied on this DDR pathway, whose inhibition halted their pro-metastatic capacity.

cancer biology↗

bioRxiv2017

MYC-driven epigenetic reprogramming favors the onset of tumorigensis by inducing a stem cell-like state

Breast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes resulted difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Over-expression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. Furthermore, we demonstrate that the MYC-driven epigenetic reprogramming favors the formation and maintenance of tumor initiating cells endowed with metastatic capacity. This study supports the notion that MYC-driven tumor initiation relies on cell reprogramming, which is mediated by the activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers.

cancer biology↗