Comparative Study of Reprogramming Efficiency and Regulatory Mechanisms of Placental- and Fibroblast-Derived Induced Pluripotent Stem Cells (iPSCs) in Mules

  • Curr Issues Mol Biol. 2025 Aug 19;47(8):671. doi: 10.3390/cimb47080671.
Fangyuan Liu  1  2  3 ,  Jia Zhang  1  2  4 ,  Lingyu Kong  5 ,  Rihan Wu  1  2  6 ,  Qiqi Jiang  1  2  6 ,  Ying Lu  5 ,  Xihe Li  1  2  3  6
Affiliations
  • 1. State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
  • 2. Research Center for Animal Genetic Resources of Mongolia·Plateau, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
  • 3. Inner Mongolia SaiKexing, Institute of Breeding and Reproductive Biotechnology in Domestic Animal, Hohhot 011517, China.
  • 4. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311113, China.
  • 5. College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China.
  • 6. National Center of Technology Innovation for Dairy Industry, Hohhot 010020, China.
PMID: 40864824 DOI: 10.3390/cimb47080671
Abstract

As an interspecies hybrid inheriting genetic material from horse and donkey lineages, mules provide a unique model for studying allele-specific regulatory dynamics. Here, we isolated adult fibroblasts (AFs) and placental fibroblasts (PFs) from mule tissues and reprogrammed them into induced pluripotent stem cells (iPSCs). Intriguingly, placental fibroblast-derived iPSCs (mpiPSCs) exhibited reduced reprogramming efficiency compared to adult fibroblast-derived iPSCs (maiPSCs). Through allele-specific expression (ASE) analysis, we systematically dissected transcriptional biases in parental cell types and their reprogrammed counterparts, revealing conserved preferential expression of asinine alleles in core pluripotency regulators (e.g., POU5F1/OCT4, SOX2, NANOG) across both cell lineages. Strikingly, mpiPSCs displayed stronger asinine allele dominance than maiPSCs, suggesting tissue-specific parental genomic imprinting. Mechanistic exploration implicated PI3K-AKT signaling as a potential pathway mediating the reprogramming inefficiency in placental fibroblasts. By integrating transcriptomic profiling with ASE technology, this study uncovers allele selection hierarchies during somatic cell reprogramming in hybrids and establishes a framework for understanding how parental genomic conflicts shape pluripotency establishment. These findings advance interspecies iPSC research by delineating allele-specific regulatory networks and providing insights into the molecular constraints of hybrid cellular reprogramming.

Keywords
ASE; PI3K-AKT; iPSCs; interspecies hybrid; pluripotency; reprogramming.
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