Biology subjects

Kasemeier-Kulesa, J. C.

Publications and source records attributed to Kasemeier-Kulesa, J. C..

3 recordsLinked to original sources

bioRxiv2024

Identification of Neural Crest and Neural Crest-Derived Cancer Cell Invasion and Migration Genes Using High-throughput Screening and Deep Attention Networks

BackgroundCell migration and invasion are well-coordinated processes in development and disease but remain poorly understood. We previously showed that highly migratory neural crest (NC) cells share a 45-gene panel with other cell invasion phenomena, including cancer. To identify critical genes of the 45-gene panel, we performed a high-throughput siRNA screen and used statistical and deep learning methods to compare NC- versus non-NC-derived human cell lines. ResultsWe find 14 out of 45 genes significantly reduces c8161 melanoma cell migration; only 4 are shared with HT1080 fibrosarcoma cells (BMP4, ITGB1, KCNE3, RASGRP1). Deep learning attention network analysis identified distinct cell-cell interaction patterns and significant alterations after BMP4 or RASGRP1 knockdown in c8161 cells. Addition of recombinant proteins to the culture media identified 5 out of the 10 known secreted molecules stimulate c8161 cell migration, including BMP4. BMP4 siRNA knockdown inhibited c8161 cell invasion in vivo and in vitro; however, its addition to the culture media rescued c8161 cell invasion. ConclusionA high-throughput screen and deep learning rapidly distilled a 45-gene panel to a small subset of genes that appear critical to melanoma cell invasion and warrant deeper in vivo functional analysis for their role in driving the neural crest.

developmental biology↗

bioRxiv2020

Transcriptome profiling of the branchial arches reveals cell type composition and a conserved signature of neural crest cell invasion

The vertebrate branchial arches that give rise to structures of the head, neck, and heart form with very dynamic tissue growth and well-choreographed neural crest, ectoderm, and mesoderm cell dynamics. Although this morphogenesis has been studied by marker expression and fate-mapping, the mechanisms that control the collective migration and diversity of the neural crest and surrounding tissues remain unclear, in part due to the effects of averaging and need for cell isolation in conventional transcriptome analysis experiments of multiple cell populations. We used label free single cell RNA sequencing on 95,000 individual cells at 2 developmental stages encompassing formation of the first four chick branchial arches to measure the transcriptional states that define the cellular hierarchy and invasion signature of the migrating neural crest. The results confirmed basic features of cell type diversity and led to the discovery of many novel markers that discriminate between axial level and distal-to-proximal cell populations within the branchial arches and neural crest streams. We identified the transcriptional signature of the most invasive neural crest that is conserved within each branchial arch stream and elucidated a set of genes common to other cell invasion signatures in types in cancer, wound healing and development. These data robustly delineate molecularly distinct cell types within the branchial arches and identify important molecular transitions within the migrating neural crest during development.

developmental biology↗

bioRxiv2019

Neural crest cells bulldoze through the microenvironment using Aquaporin-1 to stabilize filopodia

Neural crest migration requires cells to move through an environment filled with dense extracellular matrix and mesoderm to reach targets throughout the vertebrate embryo. Here, we use high-resolution microscopy, computational modeling, and in vitro and in vivo cell invasion assays to investigate the function of Aquaporin-1 (AQP-1) signaling. We find that migrating lead cranial neural crest cells express AQP-1 mRNA and protein, implicating a biological role for water channel protein function during invasion. Differential AQP-1 levels affect neural crest cell speed, direction, and the length and stability of cell filopodia. Further, AQP-1 enhances matrix metalloprotease (MMP) activity and colocalizes with phosphorylated focal adhesion kinases (pFAK). Co-localization of AQP-1 expression with EphB guidance receptors in the same migrating neural crest cells raises novel implications for the concept of guided bulldozing by lead cells during migration.

developmental biology↗