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Genomic analyses identify agents regulating somatotroph and lactotroph functions

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Abstract

Isolated hormone deficiency might be caused by loss of a specific type of endocrine cells, and regenerating these missing cells may provide a new option for future treatment. It is known that POU1F1 lineage cells can differentiate into thyrotroph, somatotroph, and lactotroph. However, there is no effective way of controlling pituitary stem/progenitor cells to differentiate into a specific type of endocrine cell. We thereby analyzed multiple genomic publications related to POU1F1 and pituitary development in this study to identify genes and agents regulating POU1F1 lineage cell differentiation. ANOVA analyses were performed to obtain differentially expressed genes. Ingenuity pathway analyses were performed to obtain signaling pathways, interaction networks, and upstream regulators. Venn diagram was used to determine the overlapping information between studies. Summary statistics was performed to rank genes according to their frequency of occurrence in these studies. The results from upstream analyses indicated that 326 agents may regulate pituitary cell differentiation. These agents can be categorized into 12 groups, including hormones and related pathways, PKA-cAMP pathways, p53/DNA damaging/cell cycle pathways, immune/inflammation regulators, growth factor and downstream pathways, retinoic/RAR pathways, ROS pathways, histone modifications, CCAAT/enhancer binding protein family, neuron development/degeneration pathways, calcium related and fat acid, and glucose pathways. Additional experiments demonstrated that H2O2 and catalase differentially regulate growth hormone and prolactin expression in somatolactotroph cells, confirming potential roles of ROS pathway on regulating somatotroph and lactotroph functions.

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Correspondence to Yunguang Tong.

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Funding

This work was supported by the National Natural Science Foundation (grant numbers 81372216 and 81160405), National Cancer Institute of the National Institutes of Health (grant numbers R00CA138914), and Jian Ding Academician workstation of Yunnan Province.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Additional information

Jun Fan and Cui Zhang contributed equally to this work.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

ESM 1

Supplemental data 1 Differentially expressed genes between pituitaries of WT and Pou1f1 mice. (XLSX 167 kb)

ESM 2

Supplemental data 2 Differentially expressed genes between chicken pituitaries of embryo days 12 and 10. (XLSX 23 kb)

ESM 3

Supplemental data 3 Differentially expressed genes between chicken pituitaries of embryo days 14 and 12. (XLSX 26 kb)

ESM 4

Supplemental data 4 Differentially expressed genes between chicken pituitaries of embryo days 17 and 14. (XLSX 29 kb)

ESM 5

Supplemental data 5 Differentially expressed genes between GH4C1 cell overexpressing Pou1f1 R271W and control cells. (XLSX 314 kb)

ESM 6

Supplemental data 6 Pou1f1 targeted genes identified using ChIP-Chip in pituitaries of pregnant mice. (XLSX 182 kb)

ESM 7

Supplemental data 7 Canonical pathways identified using Ingenuity Pathway Analysis. (XLSX 30 kb)

ESM 8

Supplemental data 8 Upstream regulating agents identified using Ingenuity Pathway Analysis. (XLSX 287 kb)

ESM 9

Supplemental data 9 Upstream regulating agents specific for each study. (XLSX 28 kb)

ESM 10

Supplemental data 10 Interaction networks of each study. (XLSX 14 kb)

ESM 11

Supplemental data 11 Appearance frequency of the components of interaction networks. (XLSX 119 kb)

ESM 12

Supplemental data 12 Detailed component information of interaction networks of each study. (PDF 7233 kb)

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Fan, J., Zhang, C., Chen, Q. et al. Genomic analyses identify agents regulating somatotroph and lactotroph functions. Funct Integr Genomics 16, 693–704 (2016). https://doi.org/10.1007/s10142-016-0518-8

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  • DOI: https://doi.org/10.1007/s10142-016-0518-8

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