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Background: In the course of animal developmental processes, various tissues are differentiated through complex interactions within the gene regulatory network. As a general concept, differentiation has been considered to be the endpoint of specification processes. Previous works followed this view and provided a genetic control scheme of differentiation in sea urchin embryos: early specification genes generate distinct regulatory territories in an embryo to express a small set of differentiation driver genes; these genes eventually stimulate the expression of tissue-specific effector genes, which provide biological identity to differentiated cells, in each region. However, some tissue-specific effector genes begin to be expressed in parallel with the expression onset of early specification genes, raising questions about the simplistic regulatory scheme of tissue-specific effector gene expression and the current concept of differentiation itself.
Results: Here, we examined the dynamics of effector gene expression patterns during sea urchin embryogenesis. Our transcriptome-based analysis indicated that many tissue-specific effector genes begin to be expressed and accumulated along with the advancing specification GRN in the distinct cell lineages of embryos. Moreover, we found that the expression of some of the tissue-specific effector genes commences before cell lineage segregation occurs.
Conclusions: Based on this finding, we propose that the expression onset of tissue-specific effector genes is controlled more dynamically than suggested in the previously proposed simplistic regulation scheme. Thus, we suggest that differentiation should be conceptualized as a seamless process of accumulation of effector expression along with the advancing specification GRN. This pattern of effector gene expression may have interesting implications for the evolution of novel cell types.
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http://dx.doi.org/10.1186/s13227-023-00210-2 | DOI Listing |
Front Immunol
September 2025
Immunocore Ltd., Abingdon, United Kingdom.
Background: The programmed cell death protein 1 (PDCD1 or PD-1) is a key regulatory immune checkpoint and a major target for therapeutic intervention. In oncology, antibodies blocking the PD-1 pathway are used to activate immune cells to promote anti tumour immunity while in immune-mediated inflammatory diseases, PD-1 agonist molecules have the potential to achieve immune suppression. NK cells are a specialised population of innate lymphocytes able to recognize a large range of distressed cells including damaged tissues in autoimmune and inflammatory conditions.
View Article and Find Full Text PDFbioRxiv
August 2025
Laboratory of Mucosal Immunology, Rockefeller University, New York, NY 10063, USA.
Pathogen-specific CD4 T cells undergo dynamic expansion and contraction during infection, ultimately generating memory clones that shape the subsequent immune responses. However, the influence of distinct tissue environments on the differentiation and clonal selection of polyclonal T cells remains unclear, primarily because of the technical challenges in tracking these cells in vivo. To address this question, we generated Tracking Recently Activated Cell Kinetics (TRACK) mice, a dual-recombinase fate-mapping system that enables precise spatial and temporal labeling of recently activated CD4 T cells.
View Article and Find Full Text PDFDiabetes Res Clin Pract
September 2025
Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011 Hunan, China. Electronic address:
Obesity is a complex chronic metabolic disease closely associated with inflammatory responses and insulin resistance. As a member of the IL-1 cytokine family, Interleukin-33(IL-33) binds to its receptor suppression of tumorigenicity 2 (ST2) and plays a crucial role in regulating the adipose tissue immune microenvironment and maintaining metabolic homeostasis. However, its role in obesity exhibits spatiotemporal specificity and functional paradoxes.
View Article and Find Full Text PDFFront Immunol
September 2025
Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
Tissue-resident memory T cells (TRM) represent a heterogeneous population of T cells that exhibit both effector and memory functionalities. They express specific gene signatures that enable them to occupy tissues without recirculating, thus providing a first response against reencountered pathogens or antigens. TRM have been implicated in the pathogenesis of various diseases, including autoimmune disorders, infections, and cancers.
View Article and Find Full Text PDFT cell immunity depends on the precise coordination of signaling networks with actin cytoskeleton remodeling, yet the molecular regulators of these processes remain incompletely defined. Flightless-1 (FLII) is a gelsolin-family actin regulator with unique leucine-rich repeats that can couple cytoskeletal dynamics to diverse signaling pathways. Here, using conditional knockout mice, we identify essential roles for FLII in both CD8⁺ and regulatory T cells.
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