Project description:Mammalian inner ear and fish lateral line sensory hair cells depend on fluid motion to transduce environmental signals and elicit a response. In mammals, actively maintained ionic homeostasis of the cochlear and vestibular fluid (endolymph) is essential for hair cell function and numerous mammalian hearing and vestibular disorders arise from disrupted endolymph ion homeostasis. Lateral line hair cells, however, are openly exposed to the aqueous environment with fluctuating ionic composition. How sensory transduction in the lateral line is maintained during environmental changes of ionic composition is not fully understood. Using lineage labeling, in vivo time lapse imaging and scRNA-seq, we discovered highly motile skin-derived cells that invade mature mechanosensory organs of the zebrafish lateral line and differentiate into Neuromast-associated (Nm) ionocytes. Furthermore, the invasive behavior is adaptive as it is triggered by drastic fluctuations in environmental stimuli. Our findings challenge the notion of an entirely placodally-derived lateral line and identify Nm ionocytes as likely regulators of mechanosensory hair cell function possibly by modulating the ionic microenvironment. The discovery of lateral line ionocytes provides an experimentally accessible in vivo system to study cell invasion and migration, as well as the physiological adaptation of vertebrate organs to changing environmental conditions.
Project description:The omentum, a visceral adipose tissue critical for metabolic, immunological, and stem cell functions, is a key site for ovarian cancer metastasis. However, its role in homeostasis and response to metastasis is not fully understood. Using single-cell transcriptomics, we profiled different omental regions in patients with benign conditions and ovarian cancer metastasis. We found that the benign omentum maintains stable cell composition and a stem cell niche. Metastasis led to immune landscape diversification and loss of mesothelial and progenitor cells. The lesser omentum, often spared in surgery, emerged as a premetastatic niche with neutrophil infiltration, NETosis, and micrometastases. Cancer cells orchestrated reprogramming of resident cells, inducing regulatory, anti-adipogenic, and immunosuppressive phenotypes across the omentum. This cell atlas illuminates the cellular and molecular determinants of organ homeostasis and reveals a high degree of plasticity and cellular reprogramming promoted by cancer colonization.