skip to main content


The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 11:00 PM ET on Thursday, June 13 until 2:00 AM ET on Friday, June 14 due to maintenance. We apologize for the inconvenience.

Title: MARS: discovering novel cell types across heterogeneous single-cell experiments
Award ID(s):
1918940 1835598 2030477 2030459
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Nature Methods
Page Range / eLocation ID:
1200 to 1206
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Intracellular protein gradients serve a variety of functions, such as the establishment of cell polarity or to provide positional information for gene expression in developing embryos. Given that cell size in a population can vary considerably, for the protein gradients to work properly they often have to be scaled to the size of the cell. Here, we examine a model of protein gradient formation within a cell that relies on cytoplasmic diffusion and cortical transport of proteins toward a cell pole. We show that the shape of the protein gradient is determined solely by the cell geometry. Furthermore, we show that the length scale over which the protein concentration in the gradient varies is determined by the linear dimensions of the cell, independent of the diffusion constant or the transport speed. This gradient provides scale-invariant positional information within a cell, which can be used for assembly of intracellular structures whose size is scaled to the linear dimensions of the cell, such as the cytokinetic ring and actin cables in budding yeast cells.

    more » « less
  2. Intermediate cell states (ICSs) during the epithelial–mesenchymal transition (EMT) are emerging as a driving force of cancer invasion and metastasis. ICSs typically exhibit hybrid epithelial/mesenchymal characteristics as well as cancer stem cell (CSC) traits including proliferation and drug resistance. Here, we analyze several single-cell RNA-seq (scRNA-seq) datasets to investigate the relation between several axes of cancer progression including EMT, CSC traits, and cell–cell signaling. To accomplish this task, we integrate computational methods for clustering and trajectory inference with analysis of EMT gene signatures, CSC markers, and cell–cell signaling pathways, and highlight conserved and specific processes across the datasets. Our analysis reveals that “standard” measures of pluripotency often used in developmental contexts do not necessarily correlate with EMT progression and expression of CSC-related markers. Conversely, an EMT circuit energy that quantifies the co-expression of epithelial and mesenchymal genes consistently increases along EMT trajectories across different cancer types and anatomical locations. Moreover, despite the high context specificity of signal transduction across different cell types, cells undergoing EMT always increased their potential to send and receive signals from other cells. 
    more » « less