Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development

Shu Zhang, Yueli Cui, Xinyi Ma, Jun Yong, Liying Yan, Ming Yang, Jie Ren, Fuchou Tang, Lu Wen () and Jie Qiao ()
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Shu Zhang: Peking University
Yueli Cui: Peking University
Xinyi Ma: Peking University
Jun Yong: Peking University
Liying Yan: Peking University
Ming Yang: Peking University
Jie Ren: Peking University
Fuchou Tang: Peking University
Lu Wen: Peking University
Jie Qiao: Peking University

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.

Date: 2020
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DOI: 10.1038/s41467-020-19012-4

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