从单个胚胎培育活体猴子及其基因匹配的胚胎干细胞。

Production of live monkeys and their genetically matched embryonic stem cells from single embryos.

作者信息

Si Chenyang, Zhu Ran, Wu Junmo, Chen Zhenzhen, Tang Zengli, Li Zuoyao, Kang Yu, Xiang Lifeng, Zuo Jiawei, Yang Pengpeng, Chu Chu, Yang Shanshan, Li Zifan, Zhao Lu, Chen Xinglong, Pu Youwei, Tian Baohong, Yang Zhaohui, Ji Weizhi, Dai Shaoxing, Niu Yuyu

机构信息

State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, China.

出版信息

Nat Commun. 2025 Jul 1;16(1):5529. doi: 10.1038/s41467-025-60694-5.

DOI:10.1038/s41467-025-60694-5

PMID:40593544

Abstract

Immune rejection poses a challenge in stem cell therapy, especially with allogeneic embryonic stem cells (ESCs). Non-human primates offer a promising avenue for developing genetically matched ESCs for regenerative medicine. Here, we successfully derive three live monkeys and their genetically matched autologous ESCs (aESCs) using embryo splitting. Additionally, from fibroblasts of one of these monkeys, we generate induced pluripotent stem cells (iPSCs) and nuclear transfer embryonic stem cells (ntESCs), creating a set of genetically matched aESCs, iPSCs, and ntESCs. Single-cell RNA-seq analysis reveals that aESCs potentially exhibit reduced heterogeneity, lower transcriptional noise, and enhanced genomic stability compared to iPSCs and ntESCs. Furthermore, we successfully derive ESCs from human split embryos, highlighting the potential for obtaining human aESCs. Collectively, our study offers an avenue for establishing autologous pluripotent stem cells and provides the theoretical basis as well as research model for further application of aESCs in human regenerative medicine.

摘要

免疫排斥在干细胞治疗中构成挑战，尤其是对于同种异体胚胎干细胞（ESC）而言。非人灵长类动物为开发用于再生医学的基因匹配ESC提供了一条有前景的途径。在此，我们通过胚胎分割成功培育出三只存活的猴子及其基因匹配的自体胚胎干细胞（aESC）。此外，从其中一只猴子的成纤维细胞中，我们生成了诱导多能干细胞（iPSC）和核移植胚胎干细胞（ntESC），创建了一组基因匹配的aESC、iPSC和ntESC。单细胞RNA测序分析表明，与iPSC和ntESC相比，aESC可能表现出更低的异质性、更低的转录噪声和更高的基因组稳定性。此外，我们成功地从人类分割胚胎中获得了ESC，突出了获取人类aESC的潜力。总体而言，我们的研究为建立自体多能干细胞提供了一条途径，并为aESC在人类再生医学中的进一步应用提供了理论基础和研究模型。