Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees

Abstract Animal behavior is linked to the gene regulatory network (GRN) coordinating gene expression in the brain. Eusocial honeybees, with their natural behavioral plasticity, provide an excellent model for exploring the connection between brain activity and behavior. Using single-nucleus RNA seque...

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Main Authors: Xiaohuan Mu, Zijing Zhang, Qun Liu, Jie Ma, Yating Qin, Haoyu Lang, Yingying Zhang, Nannan Zhang, Qunfei Guo, Pei Zhang, Denghui Li, Ruihua Zhang, Qianyue Ji, Aijun Jiang, Yang Wang, Shanshan Pan, Xiawei Liu, Xuemei Liu, Jiahui Sun, Yan Liu, Hao Chen, Li Zheng, Liang Meng, Haorong Lu, He Zhang, Yifan Zhai, Qiye Li, Junnian Liu, Huanming Yang, Jian Wang, Xiaosong Hu, Xun Xu, Shanshan Liu, Hao Zheng
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58614-8
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author Xiaohuan Mu
Zijing Zhang
Qun Liu
Jie Ma
Yating Qin
Haoyu Lang
Yingying Zhang
Nannan Zhang
Qunfei Guo
Pei Zhang
Denghui Li
Ruihua Zhang
Qianyue Ji
Aijun Jiang
Yang Wang
Shanshan Pan
Xiawei Liu
Xuemei Liu
Jiahui Sun
Yan Liu
Hao Chen
Li Zheng
Liang Meng
Haorong Lu
He Zhang
Yifan Zhai
Qiye Li
Junnian Liu
Huanming Yang
Jian Wang
Xiaosong Hu
Xun Xu
Shanshan Liu
Hao Zheng
author_facet Xiaohuan Mu
Zijing Zhang
Qun Liu
Jie Ma
Yating Qin
Haoyu Lang
Yingying Zhang
Nannan Zhang
Qunfei Guo
Pei Zhang
Denghui Li
Ruihua Zhang
Qianyue Ji
Aijun Jiang
Yang Wang
Shanshan Pan
Xiawei Liu
Xuemei Liu
Jiahui Sun
Yan Liu
Hao Chen
Li Zheng
Liang Meng
Haorong Lu
He Zhang
Yifan Zhai
Qiye Li
Junnian Liu
Huanming Yang
Jian Wang
Xiaosong Hu
Xun Xu
Shanshan Liu
Hao Zheng
author_sort Xiaohuan Mu
collection DOAJ
description Abstract Animal behavior is linked to the gene regulatory network (GRN) coordinating gene expression in the brain. Eusocial honeybees, with their natural behavioral plasticity, provide an excellent model for exploring the connection between brain activity and behavior. Using single-nucleus RNA sequencing and spatial transcriptomics, we analyze the expression patterns of brain cells associated with the behavioral maturation from nursing to foraging. Integrating spatial and cellular data uncovered cell-type and spatial heterogeneity in GRN organization. Interestingly, the stripe regulon is explicitly activated in foragers’ small Keyon cells, which are implicated in spatial learning and navigation. When worker age is controlled in artificial colonies, stripe and its key targets remained highly expressed in the KC regions of bees performing foraging tasks. These findings suggest that specific GRNs coordinate individual brain cell activity during behavioral transitions, shedding light on GRN-driven brain heterogeneity and its role in the division of labor of social life.
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publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-4256ca55b355492ea92a6125148ddb592025-08-20T03:10:10ZengNature PortfolioNature Communications2041-17232025-04-0116111610.1038/s41467-025-58614-8Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybeesXiaohuan Mu0Zijing Zhang1Qun Liu2Jie Ma3Yating Qin4Haoyu Lang5Yingying Zhang6Nannan Zhang7Qunfei Guo8Pei Zhang9Denghui Li10Ruihua Zhang11Qianyue Ji12Aijun Jiang13Yang Wang14Shanshan Pan15Xiawei Liu16Xuemei Liu17Jiahui Sun18Yan Liu19Hao Chen20Li Zheng21Liang Meng22Haorong Lu23He Zhang24Yifan Zhai25Qiye Li26Junnian Liu27Huanming Yang28Jian Wang29Xiaosong Hu30Xun Xu31Shanshan Liu32Hao Zheng33College of Food Science and Nutritional Engineering, China Agricultural UniversityCollege of Life Sciences, Hebei Normal UniversityBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-Qingdao, BGICollege of Food Science and Nutritional Engineering, China Agricultural UniversityBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-ShenzhenBGI Research-ShenzhenBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-ShenzhenBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIBGI Research-Qingdao, BGIInstitute of Plant Protection, Shandong Academy of Agricultural SciencesInstitute of Plant Protection, Shandong Academy of Agricultural SciencesInstitute of Plant Protection, Shandong Academy of Agricultural SciencesBGI Research-Qingdao, BGIBGI Research-ShenzhenBGI Research-ShenzhenInstitute of Plant Protection, Shandong Academy of Agricultural SciencesBGI Research-ShenzhenBGI Research-Qingdao, BGIBGI Research-ShenzhenBGI Research-ShenzhenCollege of Food Science and Nutritional Engineering, China Agricultural UniversityBGI Research-ShenzhenBGI Research-Qingdao, BGICollege of Food Science and Nutritional Engineering, China Agricultural UniversityAbstract Animal behavior is linked to the gene regulatory network (GRN) coordinating gene expression in the brain. Eusocial honeybees, with their natural behavioral plasticity, provide an excellent model for exploring the connection between brain activity and behavior. Using single-nucleus RNA sequencing and spatial transcriptomics, we analyze the expression patterns of brain cells associated with the behavioral maturation from nursing to foraging. Integrating spatial and cellular data uncovered cell-type and spatial heterogeneity in GRN organization. Interestingly, the stripe regulon is explicitly activated in foragers’ small Keyon cells, which are implicated in spatial learning and navigation. When worker age is controlled in artificial colonies, stripe and its key targets remained highly expressed in the KC regions of bees performing foraging tasks. These findings suggest that specific GRNs coordinate individual brain cell activity during behavioral transitions, shedding light on GRN-driven brain heterogeneity and its role in the division of labor of social life.https://doi.org/10.1038/s41467-025-58614-8
spellingShingle Xiaohuan Mu
Zijing Zhang
Qun Liu
Jie Ma
Yating Qin
Haoyu Lang
Yingying Zhang
Nannan Zhang
Qunfei Guo
Pei Zhang
Denghui Li
Ruihua Zhang
Qianyue Ji
Aijun Jiang
Yang Wang
Shanshan Pan
Xiawei Liu
Xuemei Liu
Jiahui Sun
Yan Liu
Hao Chen
Li Zheng
Liang Meng
Haorong Lu
He Zhang
Yifan Zhai
Qiye Li
Junnian Liu
Huanming Yang
Jian Wang
Xiaosong Hu
Xun Xu
Shanshan Liu
Hao Zheng
Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
Nature Communications
title Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
title_full Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
title_fullStr Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
title_full_unstemmed Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
title_short Single-nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
title_sort single nucleus and spatial transcriptomics identify brain landscape of gene regulatory networks associated with behavioral maturation in honeybees
url https://doi.org/10.1038/s41467-025-58614-8
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