CellCover defines marker gene panels capturing developmental progression in neocortical neural stem cell identity

eLife

卷:14

Neuroscience

Lanlan Ji¹  An Wang¹  Shreyash Sonthalia²  Seungmae Seo³  Daniel Q Naiman¹  Laurent Younes^1,4  Carlo Colantuoni^2,5  Donald Geman^1,4 

[1] Center for Imaging Science, Johns Hopkins University, Baltimore, United States

[2] Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, United States

[3] Departments of Neurology and Neuroscience, Johns Hopkins University, Baltimore, United States

[4] Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, United States

[5] Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, United States

关键词: human;    primate;    mouse;    single-cell RNA-seq;    marker genes;    neocortex;    Human;   

DOI  :  10.7554/eLife.107531

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Defining cell classes is central to the analysis of growing single-cell RNA sequencing (scRNA-seq) atlases. Marker genes are most often identified by differential expression (DE) methods that assess genes one at a time, ignoring the redundancy and complementarity revealed when genes are considered jointly. Working with binarized expression data, we instead seek discriminating panels of genes that together are specific to a cell type, framing marker-panel selection as a variant of the minimal set-covering problem in combinatorial optimization. This formulation efficiently searches the vast space of candidate panels, exploits the large cell numbers typical of scRNA-seq, and is robust to zero-inflation. Using blood and brain data, we show that our method, CellCover, reduces gene redundancy and captures cell-class-specific signals distinct from those found by DE. Transfer-learning experiments across mouse, primate, and human data demonstrate that CellCover identifies conserved cell classes in neocortical neurogenesis and tracks developmental progression in progenitors and neurons. Examining outer radial glia markers across mammals, we find that transcriptomic elements of this key cell type likely arose in rodent gliogenic precursors before the full program emerged in the primate lineage.

【 授权许可】

CC BY   
© 2025, Ji, Wang et al

【 图 表 】

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