Biology subjects

Tran, N. T. T.

Publications and source records attributed to Tran, N. T. T..

4 recordsLinked to original sources

bioRxiv2025

prdm1a drives a fate switch between hair cells of different mechanosensory organs

Vertebrate mechanosensory hair cells (HCs) in the ear detect sound and gravitational forces. Additionally, fish have homologous lateral line HCs in the skin that detect water vibrations for orientation and predator avoidance. HCs in fish and other non-mammalian vertebrates regenerate to restore function after damage, but mammalian HCs lack this ability, causing deafness and vestibular defects. Experimental attempts at regeneration in mice result in incomplete differentiation of immature HCs. Despite differences in regeneration, the gene regulatory networks (GRNs) driving HC maturation are highly similar across vertebrates. Here, we show that the transcription factor prdm1a plays a key role in the HC fate GRN in the zebrafish lateral line. Mutating prdm1a respecifies lateral line HCs into ear HCs, altering morphology and transcriptome. Understanding how transcription factors control diverse HC fates in zebrafish is crucial for understanding the yet unsolved regeneration of diverse HCs in mammalian ears to restore hearing and balance.

developmental biology↗

bioRxiv2024

Systemic inflammation and lymphocyte activation precede rheumatoid arthritis

Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical at-risk state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients. Our findings characterize pathogenesis prior to clinical diagnosis and suggest the at-risk state exhibits substantial immune alterations that could potentially be targeted for early intervention to delay or prevent autoimmunity. We provide a suite of tools at https://apps.allenimmunology.org/aifi/insights/ra-progression/ to facilitate exploration and enhance accessibility of this extensive dataset. One Sentence SummaryACPA+ at-risk individuals show RA-like inflammation and multi-compartment immune dysregulation during transition to clinically active RA

immunology↗

bioRxiv2021

an anti-inflammatory activation sequence governs macrophage transcriptional dynamics during tissue injury

Macrophages are essential for tissue repair and regeneration. Yet, the molecular programs, as well as the timing of their activation during and after tissue injury are poorly defined. Using a high spatio-temporal resolution single cell analysis of macrophages coupled with live imaging after sensory hair cell death in zebrafish, we find that the same population of macrophages transitions through a sequence of three major anti-inflammatory activation states. Macrophages first show a signature of glucocorticoid activation, then IL10 signaling and finally the induction of oxidative phosphorylation by IL4/Polyamine signaling. Importantly, loss-of-function of glucocorticoid and IL10 signaling shows that each step of the sequence is independently activated. Our results provide the first evidence that macrophages, in addition to a switch from M1 to M2, sequentially and independently transition though three anti-inflammatory pathways in vivo during tissue injury in a regenerating organ. One-Sentence SummaryWe show that macrophages are sequentially activated by three different anti-inflammatory pathways during tissue injury.

immunology↗

bioRxiv2021

High-resolution single cell transcriptome analysis of zebrafish sensory hair cell regeneration

Loss of sensory hair cells in the mammalian inner ear leads to permanent hearing and vestibular defects, whereas loss of hair cells in zebrafish results in their regeneration. We used scRNA-Seq to characterize the transcriptional dynamics of hair cell regeneration in zebrafish at unprecedented spatio-temporal resolution. We uncovered three, sequentially activated modules. First, an injury/inflammatory response and downregulation of progenitor/stem cell maintenance genes within minutes after hair cell loss. Second, the transient activation of regeneration-specific genes. And third, a robust reactivation of developmental gene programs, including hair cell specification, cell cycle activation, ribosome biogenesis, and a metabolic switch to oxidative phosphorylation. The results are not only relevant for our understanding of hair cell regeneration and how we might be able to trigger it in mammals but also for regenerative processes in general. The data is searchable and publicly accessible via a web-based interface.

developmental biology↗