Endocrine Unity and Diversity: A Cross-Tissue Single-Cell Regulatory Atlas

Juanru Guo, Ronghan Li, Ting Wang, Robi Mitra, Brian Muegge

Keywords: Endocrine cells, Cross-tissue single-cell atlas, Single-cell Data Integration, Regulatory programs

TL;DR: This study built a cross-tissue human endocrine atlas from 17 datasets, revealing shared secretory and unique tissue-specific regulatory programs.

Abstract: The regulatory architecture of endocrine cells—key coordinators of systemic physiology—remains poorly defined across tissues. We built a cross-tissue single-cell atlas by integrating 17 human scRNA-seq datasets from diverse organs. Using scVI for robust harmonization, we combined network inference and consensus nonnegative matrix factorization (cNMF) to resolve transcriptional programs. We uncover a hierarchical landscape in which tissue-specific, hormone-identity modules are layered on conserved pan-endocrine programs that support high secretory capacity. In particular, we identify conserved endoplasmic reticulum stress/unfolded-protein-response (UPR) and secretory-granule-biogenesis modules that form a shared backbone for hormone production and trafficking. A transcription-factor–centric analysis shows that regulatory networks mirror developmental origins and are shaped by combinatorial codes of broadly acting pan-endocrine regulators together with tissue-restricted factors. This atlas provides a foundation for probing endocrine diversity and coordination in physiology and disease.

Submission Number: 161