Biology subjects

Abidi, S. N. F.

Publications and source records attributed to Abidi, S. N. F..

4 recordsLinked to original sources

bioRxiv2025

Acute Pericentral Liver Injury Induces a Novel Transient Hepatocyte Population

The liver exhibits robust regenerative capacity in response to injury, a property shaped by its essential metabolic and detoxification roles. While the mechanisms of regeneration following chronic liver injury have been extensively studied, the response during the early phases of acute injury remains poorly understood. Here, we employed a pericentral model of acute liver injury using carbon tetrachloride (CCl4) to investigate the initial hepatocyte response to damage. Through integration of single-nucleus multiome-sequencing, lineage tracing, spatial transcriptomics, and immunostaining, we identified a novel, transient population of damage-responsive SOX9+ pericentral hepatocytes. This population does not exhibit progenitor-like behavior but instead potentially mediates key aspects of early tissue repair. Specifically, SOX9+ pericentral hepatocytes engage in interactions with hepatic stellate cells and display migratory features associated with wound closure. Moreover, these cells exhibit an immune-related transcriptional signature and colocalize with liver macrophages at injury sites, suggesting a role in modulating immune responses. Our findings highlight a previously underappreciated function of SOX9 as a stress-responsive regulator of hepatocyte behavior and intercellular crosstalk during the early stages of acute liver injury.

cell biology↗

bioRxiv2024

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation

The sebaceous gland (SG) is a vital appendage of the epidermis, and its normal homeostasis and function is crucial for effective maintenance of the skin barrier. Notch signaling is a well-known regulator of epidermal differentiation, and has also been shown to be involved in postnatal maintenance of SGs. However, the precise role of Notch signaling in regulating SG differentiation in the adult homeostatic skin remains unclear. While there is evidence to suggest that Notch1 is the primary Notch receptor involved in regulating the differentiation process, the ligand remains unknown. Using monoclonal therapeutic antibodies designed to specifically inhibit of each of the Notch ligands or receptors, we have identified the Jag2/Notch1 signaling axis as the primary regulator of sebocyte differentiation in homeostatic skin. Mature sebocytes are lost upon specific inhibition of the Jag2 ligand or Notch1 receptor, resulting in the accumulation of proliferative stem/progenitor cells in the SG. Strikingly, this phenotype is reversible, as these stem/progenitor cells re-enter differentiation when the inhibition of Notch activity is lifted. Thus, Notch activity promotes correct sebocyte differentiation, and is required to restrict progenitor proliferation.

developmental biology↗

bioRxiv2019

The gene brain tumor constrains growth to ensure proper patterning during regeneration in Drosophila imaginal discs

Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent overgrowth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure. Author SummaryWhile much has been published about the signals that stimulate regeneration, the mechanisms that constrain and/or terminate regeneration have not been well characterized. Thus, we do not understand what limits may exist on the rate of regenerative growth, what mechanisms constrain regeneration, and what the consequences might be of enhancing regrowth. Here, we detail our discovery and characterization of a mechanism that constrains regeneration, and the deleterious effects of reducing that constraint. In this manuscript, we describe our identification of the RNA regulator Brat as a factor that constrains regenerative growth. Without this constraint on regenerative growth, patterning mistakes occur leading to a malformed regenerated structure. We demonstrate that the patterning errors are not due to faster growth itself, but are due to the overexpression of the pro-growth transcription factor Myc.

developmental biology↗

bioRxiv2017

A Positive Feedback Loop Ensures Propagation of ROS Production and JNK Signaling Throughout Drosophila Tissue Regeneration

Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed wholegenome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescent labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by wholegenome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.\n\nAuthor summaryRegenerating tissue must initiate the signaling that drives regenerative growth, and then sustain that signaling long enough for regeneration to complete. Drosophila imaginal discs, the epithelial structures in the larva that will form the adult animal during metamorphosis, have been an important model system for tissue repair and regeneration for over 60 years. Here we show that damage-induced JNK signaling leads to the upregulation of a gene called moladietz, which encodes a co-factor for an enzyme, NADPH dual oxidase (DUOX), that generates reactive oxygen species (ROS), a key tissue-damage signal. High expression of moladietz induces continuous production of ROS in the regenerating tissue. The sustained production of ROS then continues to activate JNK signaling throughout the course of regeneration, ensuring maximal tissue regrowth.

developmental biology↗