Cross-species insights into placental evolution and diseases at the single-cell resolution

Guanghui Tan; Ao Zhang; Xuesha Cao; Jingyu Yang; Youjie Cui; Fei Wang; Tao Shi; Hengkuan Li; Haoping Wang; Huiquan Shan; Jilong Ren; Yaqi Zhou; Menghan Wang; Funong Luo; Xi Guo; Wuqiang Huo; Yingran Liu; Zhannur Niyazbekova; Xihong Wang; Zhenyu Xiao; Yi Zheng; Yu Jiang

doi:10.1038/s41467-026-72652-w

Cross-species insights into placental evolution and diseases at the single-cell resolution

Guanghui Tan
, Ao Zhang
, Xuesha Cao
, Jingyu Yang
, Youjie Cui
, Fei Wang
, Tao Shi
, Hengkuan Li
, Haoping Wang
, Huiquan Shan
, Jilong Ren
, Yaqi Zhou
, Menghan Wang
, Funong Luo
, Xi Guo
, Wuqiang Huo
, Yingran Liu
, Zhannur Niyazbekova
, Xihong Wang^*
, Zhenyu Xiao^*

Yi Zheng^*, Yu Jiang^*

^*此作品的通讯作者

Northwest Agriculture and Forestry University
Beijing Institute of Technology
Kazakh National Agrarian University

科研成果: 期刊稿件 › 文章 › 同行评审

摘要

The placenta is essential for fetal development, yet its molecular evolution across mammals remains elusive. Here, we present a comprehensive single-cell transcriptomic atlas of ~300,000 cells from ten species representing the four primary placental types: discoid, cotyledonary, diffuse, and zonary. Our cross-species analysis identifies trophoblast lineages as the primary drivers of placental diversification. By reconstructing differentiation trajectories, we elucidate the regulatory networks shaping trophoblast development across diverse architectures. We propose that the unique gene expression profile of human trophoblasts underlies the susceptibility to preeclampsia and miscarriage. Functional experiments demonstrate that TGIF1 acts as a key upstream regulator of extravillous trophoblast growth and migration. TGIF1 and its targets, including ADAM12, WNT3A, and ZNF831, are associated with preeclampsia and pregnancy loss. Collectively, this high-resolution framework provides fundamental insights into the molecular evolution of the placenta and its contribution to reproductive success and diseases.

源语言	英语
期刊论文编号	6259
期刊	Nature Communications
卷	17
期	1
DOI	https://doi.org/10.1038/s41467-026-72652-w
出版状态	已出版 - 12月 2026
已对外发布	是

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Tan, G., Zhang, A., Cao, X., Yang, J., Cui, Y., Wang, F., Shi, T., Li, H., Wang, H., Shan, H., Ren, J., Zhou, Y., Wang, M., Luo, F., Guo, X., Huo, W., Liu, Y., Niyazbekova, Z., Wang, X., ... Jiang, Y. (2026). Cross-species insights into placental evolution and diseases at the single-cell resolution. Nature Communications, 17(1), 期刊论文 6259. https://doi.org/10.1038/s41467-026-72652-w

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title = "Cross-species insights into placental evolution and diseases at the single-cell resolution",

abstract = "The placenta is essential for fetal development, yet its molecular evolution across mammals remains elusive. Here, we present a comprehensive single-cell transcriptomic atlas of \textasciitilde{}300,000 cells from ten species representing the four primary placental types: discoid, cotyledonary, diffuse, and zonary. Our cross-species analysis identifies trophoblast lineages as the primary drivers of placental diversification. By reconstructing differentiation trajectories, we elucidate the regulatory networks shaping trophoblast development across diverse architectures. We propose that the unique gene expression profile of human trophoblasts underlies the susceptibility to preeclampsia and miscarriage. Functional experiments demonstrate that TGIF1 acts as a key upstream regulator of extravillous trophoblast growth and migration. TGIF1 and its targets, including ADAM12, WNT3A, and ZNF831, are associated with preeclampsia and pregnancy loss. Collectively, this high-resolution framework provides fundamental insights into the molecular evolution of the placenta and its contribution to reproductive success and diseases.",

author = "Guanghui Tan and Ao Zhang and Xuesha Cao and Jingyu Yang and Youjie Cui and Fei Wang and Tao Shi and Hengkuan Li and Haoping Wang and Huiquan Shan and Jilong Ren and Yaqi Zhou and Menghan Wang and Funong Luo and Xi Guo and Wuqiang Huo and Yingran Liu and Zhannur Niyazbekova and Xihong Wang and Zhenyu Xiao and Yi Zheng and Yu Jiang",

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doi = "10.1038/s41467-026-72652-w",

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Tan, G, Zhang, A, Cao, X, Yang, J, Cui, Y, Wang, F, Shi, T, Li, H, Wang, H, Shan, H, Ren, J, Zhou, Y, Wang, M, Luo, F, Guo, X, Huo, W, Liu, Y, Niyazbekova, Z, Wang, X, Xiao, Z, Zheng, Y & Jiang, Y 2026, 'Cross-species insights into placental evolution and diseases at the single-cell resolution', Nature Communications, 卷 17, 号码 1, 6259. https://doi.org/10.1038/s41467-026-72652-w

TY - JOUR

T1 - Cross-species insights into placental evolution and diseases at the single-cell resolution

AU - Tan, Guanghui

AU - Zhang, Ao

AU - Cao, Xuesha

AU - Yang, Jingyu

AU - Cui, Youjie

AU - Wang, Fei

AU - Shi, Tao

AU - Li, Hengkuan

AU - Wang, Haoping

AU - Shan, Huiquan

AU - Ren, Jilong

AU - Zhou, Yaqi

AU - Wang, Menghan

AU - Luo, Funong

AU - Guo, Xi

AU - Huo, Wuqiang

AU - Liu, Yingran

AU - Niyazbekova, Zhannur

AU - Wang, Xihong

AU - Xiao, Zhenyu

AU - Zheng, Yi

AU - Jiang, Yu

PY - 2026/12

Y1 - 2026/12

N2 - The placenta is essential for fetal development, yet its molecular evolution across mammals remains elusive. Here, we present a comprehensive single-cell transcriptomic atlas of ~300,000 cells from ten species representing the four primary placental types: discoid, cotyledonary, diffuse, and zonary. Our cross-species analysis identifies trophoblast lineages as the primary drivers of placental diversification. By reconstructing differentiation trajectories, we elucidate the regulatory networks shaping trophoblast development across diverse architectures. We propose that the unique gene expression profile of human trophoblasts underlies the susceptibility to preeclampsia and miscarriage. Functional experiments demonstrate that TGIF1 acts as a key upstream regulator of extravillous trophoblast growth and migration. TGIF1 and its targets, including ADAM12, WNT3A, and ZNF831, are associated with preeclampsia and pregnancy loss. Collectively, this high-resolution framework provides fundamental insights into the molecular evolution of the placenta and its contribution to reproductive success and diseases.

AB - The placenta is essential for fetal development, yet its molecular evolution across mammals remains elusive. Here, we present a comprehensive single-cell transcriptomic atlas of ~300,000 cells from ten species representing the four primary placental types: discoid, cotyledonary, diffuse, and zonary. Our cross-species analysis identifies trophoblast lineages as the primary drivers of placental diversification. By reconstructing differentiation trajectories, we elucidate the regulatory networks shaping trophoblast development across diverse architectures. We propose that the unique gene expression profile of human trophoblasts underlies the susceptibility to preeclampsia and miscarriage. Functional experiments demonstrate that TGIF1 acts as a key upstream regulator of extravillous trophoblast growth and migration. TGIF1 and its targets, including ADAM12, WNT3A, and ZNF831, are associated with preeclampsia and pregnancy loss. Collectively, this high-resolution framework provides fundamental insights into the molecular evolution of the placenta and its contribution to reproductive success and diseases.

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DO - 10.1038/s41467-026-72652-w

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AN - SCOPUS:105045191073

SN - 2041-1723

VL - 17

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6259

ER -

Cross-species insights into placental evolution and diseases at the single-cell resolution

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