Dynamic remodeling of the transcriptional landscape drives Merkel cell specification and mechanosensory differentiation
Source: Proceedings of the National Academy of Sciences of the United States of America
Authors: Yajun Zhang, Huipu Yuan, Yuyan Jiang, Teng Wang, Chen Rui, Yuanyuan Ding, Tuan Wang, Chaochen Wang, Ying Xiao, Publication Date: Tue, 22 Sep 2026 06:00:00 -0400
Proc Natl Acad Sci U S A. 2026 Sep 29;123(39):e2603770123. doi: 10.1073/pnas.2603770123. Epub 2026 Sep 22.
ABSTRACT
Merkel cells (MCs) are specialized mechanosensory receptor cells essential for touch sensation, exhibiting both epithelial and neuroendocrine characteristics. However, the regulatory processes that shape MC fate remain poorly defined. Using single-cell RNA sequencing, we construct a conserved, triphasic atlas of MC ontogeny comprising an epithelial-like stage, a transitional intermediate phase, and a terminal neuroendocrine state. Importantly, we identify JunB as a priming factor essential for initiating MC differentiation, while Pou4f1 acts as a driver of epithelial-neuroendocrine conversion and subsequent functional integration. Moreover, the gene regulatory network analysis further reveals that TUBB3+ primed cells could differentiate into the MC lineage under the regulation of Barhl1 and Atoh1. Genetic lineage tracing and cross-species analyses validate these mechanisms. Together, our work delineates the transcriptional network orchestrating MC fate determination and mechanosensory differentiation, providing not only mechanistic insights but also highlighting actionable targets relevant to MC carcinoma and sensory restoration.
PMID:42771513 | DOI:10.1073/pnas.2603770123
Pubmed ID: pubmed:42771513
Identifiers: pmid:42771513, doi:10.1073/pnas.2603770123,
Paper chosen by Rajesh Khanna
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Zhang et al. used single-cell RNA sequencing to map how Merkel cells, the skin’s touch receptors, develop. They describe three stages: an epithelial-like start, a transitional phase and a final neuroendocrine state. JunB appears to start the process, and Pou4f1 drives the switch from epithelial to neuroendocrine identity. Barhl1 and Atoh1 guide TUBB3+ primed cells into the Merkel cell lineage. Lineage tracing and comparisons across species support these findings.
Why should you care? These genes could become treatment targets for Merkel cell carcinoma, a rare but aggressive skin cancer. They could also help restore touch after nerve injury or disease.