STOmics technology:BGI Stereomics Stereo-Seq

Data type:Spatial transcriptomics

Sample scope:Multiisolate

Summary:The causative genetic changes responsible for the loss of regeneration during mammalian evolution remain elusive. Comparative single-cell sequencing and spatial transcriptomic analyses of rabbits and mice uncovered the suppression of retinoic acid (RA) production, caused by the loss of Aldh1a2 expression and boosted RA degradation, is responsible for the failure of mouse ear pinna regeneration. Reactivation of Aldh1a2 or exogenous supplement of RA but not the synthetic precursor retinol was sufficient to switch the ear pinna repair into complete regeneration. The in vivo lineage tracing showed the restored regeneration was contributed by injury-activated Tnn+ cells. Transgenic reporter assays and a high-resolution map of 3D genome organization revealed evolutionary loss of the AE1 enhancer and injury responsiveness of Aldha1a2 promoter in mice contributed to the difficiencty of Aldh1a2 upon injury. Our study has important implications for dissecting the causative molecular mechanisms responsible for the limited regeneration in damaged human organs.

Contributor(s):Weifen Lin, Xiaohui Jia, Qiuya He, Xiaofeng Shi, Panyu Zhang et al.

Submitter:张盼玉(PanyuZhang),BGI

Release date:2025-04-30

Updated:2025-04-30