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<p>Sexual dimorphism profoundly influences adrenal physiology and disease susceptibility, yet its spatial molecular basis remains poorly understood. The female-predominant X-zone, a transient cortical structure recognized for nearly a century, has lacked comprehensive molecular characterization. Here we use Visium HD spatial transcriptomics with Cellpose-based cell segmentation to generate ~203,000 near-single-cell-resolution transcriptomic profiles from sexually mature mouse adrenal glands (four male, four female). We identify ten distinct cell populations with sex differences predominantly concentrated in inner cortical zones. The X-zone exhibits pronounced sexual dimorphism, with Akr1c18 as the primary marker (log₂FC = −16.28, female-enriched); combined use with Pik3c2g provides more robust zone identification, confirming the X-zone as a specialized progesterone-catabolizing compartment. Female adrenal glands exhibit greater intercellular communication complexity (435 vs 369 interactions) and higher aggregate signalling strength, with SPP1-integrin pathways predicted to be enriched in the female X-zone microenvironment. Spatial trajectory inference reveals a dominant centripetal gradient conserved across both sexes and a secondary centrifugal axis from the JMZ/X region prominent in females. This atlas establishes spatial restriction as a fundamental organizing principle of endocrine sexual dimorphism, with implications for precision medicine approaches to adrenal disorders.</p>

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Single-cell spatial transcriptomics reveals sex-dependent gene expression and intercellular signalling in mouse adrenal cortex

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月14日

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  • Małgorzata Blatkiewicz,
  • Szymon Hryhorowicz,
  • Marta Szyszka,
  • Joanna Suszynska-Zajczyk,
  • Andrzej Plawski,
  • Anna Olechnowicz,
  • Andrea Porzionato,
  • Ludwik K. Malendowicz,
  • Marcin Rucinski

摘要

Sexual dimorphism profoundly influences adrenal physiology and disease susceptibility, yet its spatial molecular basis remains poorly understood. The female-predominant X-zone, a transient cortical structure recognized for nearly a century, has lacked comprehensive molecular characterization. Here we use Visium HD spatial transcriptomics with Cellpose-based cell segmentation to generate ~203,000 near-single-cell-resolution transcriptomic profiles from sexually mature mouse adrenal glands (four male, four female). We identify ten distinct cell populations with sex differences predominantly concentrated in inner cortical zones. The X-zone exhibits pronounced sexual dimorphism, with Akr1c18 as the primary marker (log₂FC = −16.28, female-enriched); combined use with Pik3c2g provides more robust zone identification, confirming the X-zone as a specialized progesterone-catabolizing compartment. Female adrenal glands exhibit greater intercellular communication complexity (435 vs 369 interactions) and higher aggregate signalling strength, with SPP1-integrin pathways predicted to be enriched in the female X-zone microenvironment. Spatial trajectory inference reveals a dominant centripetal gradient conserved across both sexes and a secondary centrifugal axis from the JMZ/X region prominent in females. This atlas establishes spatial restriction as a fundamental organizing principle of endocrine sexual dimorphism, with implications for precision medicine approaches to adrenal disorders.