Single-cell transcriptomics uncovers conserved cardiac cell types and regulatory adaptation across birds and mammals

Yan Hao; Xiang Zhou; Qingshuo Zhao; Huishang She; Yun Fang; Laikun Ma; Zhengting Zou; Weiwei Zhai; Per G.P. Ericson; Fumin Lei; Fanwei Meng; Shihua Zhang; Yanhua Qu

doi:10.59717/j.xinn-life.2026.100251

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Single-cell transcriptomics uncovers conserved cardiac cell types and regulatory adaptation across birds and mammals

1.
State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2.
Guangdong Institute of Intelligence Science and Technology, Zhuhai 519031, China
3.
State Key Laboratory of Mathematical Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China
4.
Chengde Innovation Center for Exploitation and Ecological Protection of Distinctive Biological Resources, Hebei Minzu Normal University, Chengde 067000, China
5.
College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China
6.
Department of Bioinformatics and Genetics, Swedish Museum of Natural History, Stockholm SE-104 05, Sweden
7.
School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
8.
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
9.
These authors contributed equally

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Corresponding authors: quyh@ioz.ac.cn (Y.Q.); zsh@amss.ac.cn (S.Z.); mengfw@ioz.ac.cn (F.M.); leifm@ioz.ac.cn (F.L.)
Received Date: March 25, 2026

Accepted Date: September 04, 2026

Published Online: September 07, 2026

The Innovation Life https://doi.org/10.59717/j.xinn-life.2026.100251 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Eleven major cardiac cell types were identified in adult and neonatal tree sparrows.
  
  Adult and neonatal birds exhibited a substantial difference in cell abundance and transcriptional divergence.
  
  Cardiac cell types and transcriptional programs were conserved across birds and mammals.
  
  Overexpression of insulin-like growth factor 1 receptor (IGF1R) in avian cardiomyocytes induced hypertrophy.

ABSTRACT

ABSTRACT

Birds and mammals possess highly efficient four-chambered hearts to meet the elevated metabolic demands of endothermy, yet the cellular and molecular basis of this convergent evolution remains poorly understood. To address this gap, we generated the first single-cell heart transcriptomic atlas of a wild bird, the Eurasian Tree Sparrow (Passer montanus), across neonatal and adult stages, and integrated it with existing human and mouse data. This cross-species comparison reveals broadly conserved transcriptional profiles: cardiomyocytes are the most transcriptionally conserved cell type across species and developmental stages, whereas non-myocyte populations (fibroblasts and endothelial cells) show greater transcriptional plasticity. These findings suggest that cardiac diversification and adaptation may occur primarily through regulatory changes within a shared cellular repertoire. Extending this framework, we investigate cardiac adaptation to high-elevation hypoxia in tree sparrows. Strikingly, the transcriptional programs significantly overlapped with genes previously linked to cardiac remodeling and disease-related phenotypes in humans and mice. To test the functional relevance of this overlap, we performed in vitro assays and found that IGF1R overexpression drives hypertrophy-like growth in avian cardiomyocytes, accompanied by PI3K-AKT-mTOR-associated transcriptional reprogramming, a pathway critically implicated in mammalian cardiac hypertrophy. Collectively, our findings demonstrate that birds and mammals share a conserved cardiac cellular blueprint, wherein regulatory programs are recurrently co-opted during development, adaptation to hypoxia, and pathological remodeling.
- Single-cell transcriptomics /
- Cardiac adaptation /
- Convergent evolution /
- Cardiac hypertrophy /
- PI3K-AKT-mTOR signaling axis

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Hao Y., Zhou X., Zhao Q., et al. (2026). Single-cell transcriptomics uncovers conserved cardiac cell types and regulatory adaptation across birds and mammals. The Innovation Life 4:100251. https://doi.org/10.59717/j.xinn-life.2026.100251

Hao Y., Zhou X., Zhao Q., et al. (2026). Single-cell transcriptomics uncovers conserved cardiac cell types and regulatory adaptation across birds and mammals. The Innovation Life 4:100251. https://doi.org/10.59717/j.xinn-life.2026.100251

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Single-cell transcriptomics uncovers conserved cardiac cell types and regulatory adaptation across birds and mammals

GRAPHICAL ABSTRACT

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