Biology subjects

Godini, R.

Publications and source records attributed to Godini, R..

4 recordsLinked to original sources

bioRxiv2024

Transcriptional Regulatory Logic Orchestrating Lymphoid and Myeloid Cell Fate Decisions

The differentiation of hematopoietic stem cells (HSCs) into diverse blood and immune cells is a complex, highly hierarchical process characterized by a series of tightly regulated steps. It involves a sequence of intermediate oligo-potent progenitors making successive binary decisions. This process gradually narrows down lineage possibilities until a final fate is reached. This step-wise process is tightly controlled by Transcription Factors (TFs) and their associated regulome ultimately resulting the differentiation of both lymphoid and myeloid compartments. Here, we set to unravel the lineage-specific gene regulatory circuitry controlling the development of B cells, T cells, Innate Lymphoid Cells (ILCs), and Dendritic Cells (DCs). We employ Weighted Gene Co-expression Network Analysis (WGCNA) to characterize gene modules associated to the lymphoid or myeloid cell fate, enabling the identification of lineage restricted TFs based on their expression patterns. By identifying TFs whose expression is subset-restricted or those with a broader expression in the hematopoietic compartment we construct a regulatory logic that potentially controls the development of these key immune cells. Our results point to conserved regulatory elements between ILCs, Natural Killer cells, and DCs. This analysis unravels an intricate relationship between each cell types and how the expression of key TFs dictate lineage specificity. We particularly dissect the elements associated to conventional DCs and plasmacytoid DCs. In conclusion, our findings shed new lights on regulatory mechanisms controlling blood cell development and offer a blueprint that can be leveraged to better understand the molecular mechanisms underpinning blood cell development.

cell biology↗

bioRxiv2024

Dissecting the transcriptional regulation of infant and childhood acute myeloid leukemia

Pediatric acute myeloid leukemia (AML) exhibits distinct characteristics between infants and children, manifested by variations in clinical features, cytogenetic abnormalities, and molecular aberrations. While most studies have focused on the associations between genomic abnormalities, age groups, and disease status, the transcriptional profiles and gene regulatory mechanisms underlying these differences remain underexplored. In this study, through differential gene expression analysis and Weighted Gene Co-expression Network Analysis, I have identified gene groups associated with AML and further categorized them by infant and childhood subgroups. The findings reveal three distinct gene groups with age- and tissue-specific expression patterns. Additionally, I propose a gene regulatory circuitry that elucidates the differences between infant and childhood AML. Several novel markers demonstrating significant expression changes in tumors were identified. Moreover, a comprehensive gene regulatory network for pediatric AML was constructed using differentially expressed transcription factors and protein-gene interaction data. This study highlights new gene regulation mechanisms in pediatric AML and offers potential avenues for developing novel biomarkers and therapeutic strategies.

cancer biology↗

bioRxiv2023

A matrisome atlas of germ cell development

The extracellular matrix (matrisome) provides chemical and mechanical cues to control the structure and function of cells and tissues. Yet, comprehensive understanding of how matrisome factors individually and collectively control cell and tissue behavior in vivo is lacking. Here, we systematically investigate the function of 443 conserved matrisome-coding genes in controlling germ cell behavior within a complex tissue - the Caenorhabditis elegans germline. Using high-content imaging, 3D reconstruction and cell behavior analysis of >3500 germlines and >7 million germ cells, we identify specific matrisome factors that regulate germline structure, protein distribution, germ cell cycle and fate, apoptosis, and oocyte health. These findings reveal matrisome networks acting autonomously and non-autonomously to coordinate germ cell behavior, providing new avenues to study and manipulate cell fates.

cell biology↗

bioRxiv2022

Characterization of the Doublesex/MAB-3 transcription factor DMD-9 in Caenorhabditis elegans

DMD-9 is a Caenorhabditis elegans Doublesex/MAB-3 Domain transcription factor of unknown function. Single-cell transcriptomics revealed that dmd-9 is highly expressed in specific head sensory neurons, with lower levels detected in non-neuronal tissues (uterine cells and spermatheca). Here, we characterized endogenous dmd-9 expression and function in hermaphrodites and males to identify potential sexually dimorphic roles. In addition, we dissected the trans- and cis-regulatory mechanisms that control DMD-9 expression in neurons. Our results show that of the 22 DMD-9-expressing neuronal reporters we analyzed, only the neuropeptide-encoding flp-19 gene is cell-autonomously regulated by DMD-9. Further, we did not identify defects in behaviors mediated by DMD-9 expressing neurons in dmd-9 mutants. We found that dmd-9 expression in neurons is regulated by four neuronal fate regulatory TFs: ETS-5, EGL-13, CHE-1, and TTX-1. In conclusion, our study characterized the DMD-9 expression pattern and regulatory logic for its control. We found that, as with other DMD TFs, DMD-9 likely acts redundantly to control neuronal development and function.

developmental biology↗