Efficient Multi-Organ Multi-Center Cell Nuclei Segmentation Method Based on Deep Learnable Aggregation Network

Automated cell nuclei delineation in whole-slide imaging (WSI) is a fundamental step for many tasks like cancer cell recognition, cancer grading, and cancer subtype classification. Although numerous computational methods have been proposed for segmenting nuclei in WSI images based on image processing and deep learning, existing approaches face major challenges such as color variation due to the use of different stains, the various structures of cell nuclei, and the overlapping and clumped cell nuclei. To circumvent these challenges in this article, we propose an efficient and accurate cell nuclei segmentation method based on deep learning, in which a set of accurate individual cell nuclei segmentation models are developed to predict rough segmentation masks, and then a learnable aggregation network (LANet) is used to predict the final nuclei masks. Besides, we develop cell nuclei segmentation software (with a graphical user interface—GUI) that includes the proposed method and other deep-learning-based cell nuclei segmentation methods. A challenging WSI dataset collected from different centers and organs is used to demonstrate the efficiency of our method. The experimental results reveal that our method obtains a competitive performance compared to the existing approaches in terms of the aggregated Jaccard index (AJI=89.25%) and F1-score (F1=73.02%). The developed nuclei segmentation software can be downloaded from https://github.com/loaysh2010/Cell-Nuclei-Segmentation-GUI-Application.

The initiation knot is a signaling center required for molar tooth development

ABSTRACT Signaling centers, or organizers, regulate many aspects of embryonic morphogenesis. In the mammalian molar tooth, reiterative signaling in specialized centers called enamel knots (EKs) determines tooth patterning. Preceding the primary EK, transient epithelial thickening appears, the significance of which remains debated. Using tissue confocal fluorescence imaging with laser ablation experiments, we show that this transient thickening is an earlier signaling center, the molar initiation knot (IK), that is required for the progression of tooth development. IK cell dynamics demonstrate the hallmarks of a signaling center: cell cycle exit, condensation and eventual silencing through apoptosis. IK initiation and maturation are defined by the juxtaposition of cells with high Wnt activity to Shh-expressing non-proliferating cells, the combination of which drives the growth of the tooth bud, leading to the formation of the primary EK as an independent cell cluster. Overall, the whole development of the tooth, from initiation to patterning, is driven by the iterative use of signaling centers.

The Initiation Knot is a Signaling Center Required for Molar Tooth Development

SummarySignaling centers, or organizers, regulate many aspects of embryonic morphogenesis. In the mammalian molar tooth, reiterative signaling in specialized centers called enamel knots (EKs) determine tooth patterning. Preceding the first, primary EK, a transient epithelial thickening appears whose significance remains debated. Here, using tissue confocal fluorescence imaging with laser ablation experiments, we show that this transient thickening is an earlier signaling center, the molar initiation knot (IK) that is required for the progression of tooth development. IK cell dynamics manifest the hallmarks of a signaling center; cell cycle exit, condensation, and eventual silencing through apoptosis. IK initiation and maturation are defined by the juxtaposition of high Wnt activity cells to Shh-expressing non-proliferating cells, the combination of which drives the growth of the tooth bud, leading to the formation of the primary EK as an independent cell cluster. Overall, the whole development of the tooth, from initiation to patterning, is driven by the iterative use of signaling centers.