Short histological kaleidoscope - recent findings in histology. Part VI. Kupffer cells, hepatic stellate cells, enteroendocrine cells, and telocytes.

The liver, intestinal epithelium, and nervous system harbor specialized cell populations whose biology has been fundamentally redefined by contemporary histological and molecular methodologies. This review synthesizes recent advances across four such populations: Kupffer cells (KCs), hepatic stellate cells (HSCs; Ito cells), enteroendocrine cells (EECs), and telocytes (TCs). KCs are now understood as ontogenetically heterogeneous, yolk sac-derived populations maintained by local self-renewal and shaped by durable epigenomic reprogramming. Their molecular identity, anchored to species-specific markers including C-type lectin domain family 4 member F (CLEC4F), T-cell immunoglobulin and mucin domain-containing protein 4 (TIM4), V-set and immunoglobulin domain-containing protein 4 (VSIG4), and the human-specific succinate receptor 1 (SUCNR1), is dynamically regulated by sinusoidal niche signals and underlies central roles in metabolic liver disease, fibrosis, viral hepatitis, and hepatocellular carcinoma. HSCs exhibit a tightly regulated functional continuum spanning quiescence, activation, senescence, and apoptosis, with single-cell transcriptomics revealing spatially restricted subpopulations and novel cytoskeletal markers - syncoilin, synemin, and cytoglobin - adding molecular resolution to the activation-quiescence axis. EECs, though representing only 1% of intestinal epithelial cells, operate as multifunctional neuroepithelial transducers: their neuropod-mediated gut-brain connectivity, microbiota-driven epigenetic regulation, and vesicle-mediated mucosal immune modulation challenge the classical view of these cells as simple hormone-secreting units. TCs, defined by their moniliform cytoplasmic extensions termed telopodes, constitute an emerging stromal population within peripheral and central nervous system compartments, with putative roles in intercellular scaffolding, post-lesional regeneration, and tumor microenvironment organization. Collectively, these findings redefine each population as a dynamic, context-responsive entity with significant implications for the understanding and treatment of metabolic, inflammatory, fibrotic, and neoplastic diseases.