Generation of tetraploid organs in mice

	Generation of tetraploid organs in mice
	Wei, S; Zou, GW; Zhang, YY; Li, SP; Hu, M; Du, J; Liu, JW; Ran, L; Zhou, CK; Lin, JW
	2026
发表期刊	Zool. Res.
ISSN	2095-8137
卷号	47 期号:2 页码:347-360
摘要	Tetraploidy occurs infrequently in mammals but remains widespread in amphibians. Blastocyst complementation using xenogeneic transplantation of tetraploid embryonic stem cells (4N-ESCs) represents a promising approach to mitigate organ shortages, yet robust generation of fully reconstituted organs in mammalian hosts remains elusive. In this study, CRISPR/Cas9, the Cre-LoxP system, and blastocyst complementation were combined to generate tetraploid mouse liver, heart, and pancreatic tissues. 4N-ESCs (tdTomato-labeled) were established and shown to maintain stable pluripotency and tetraploidy, as confirmed by karyotyping and immunofluorescence analyses. Subsequently, these cells were microinjected into Hhexand Pdx1-deficient blastocysts and Nkx2.5 lineage-ablated blastocysts, which were engineered to lack relevant organ-forming lineages. Tetraploid pups exhibited significantly reduced body mass and organ mass (liver and heart) relative to diploid controls (P<0.05). Fluorescence-activated cell sorting demonstrated a significant 4N-ESC (tdTomato-labeled) contribution within tetraploid organs (4N population) at E18.5, with tdTomato-positive fractions reaching 84.3% of hepatic cells, 67.8% of cardiac cells, and 73.4% of pancreatic cells. Single-cell transcriptome sequencing further revealed that tetraploidy markedly altered developmental trajectories and differentiation programs in liver and heart tissues, and 4N-ESCs showed preferential integration into tetraploid liver and heart with a substantial contribution to pancreatic regeneration. Collectively, these findings support the feasibility of 4N- ESC-based blastocyst complementation for human organ regeneration and establish a framework for developing strategies to alleviate organ shortages in clinical settings.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15118
专题	科研部门_动物感觉与生存适应(罗雷）
推荐引用方式 GB/T 7714	Wei, S,Zou, GW,Zhang, YY,et al. Generation of tetraploid organs in mice[J]. Zool. Res.,2026,47(2):347-360.
APA	Wei, S.,Zou, GW.,Zhang, YY.,Li, SP.,Hu, M.,...&Lin, JW.(2026).Generation of tetraploid organs in mice.Zool. Res.,47(2),347-360.
MLA	Wei, S,et al."Generation of tetraploid organs in mice".Zool. Res. 47.2(2026):347-360.

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2026071320.pdf（15653KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文