Establishment of Bovine-Induced Pluripotent Stem Cells

Pluripotent stem cells (PSCs) have been successfully developed in many species. However, the establishment of bovine-induced pluripotent stem cells (biPSCs) has been challenging. Here we report the generation of biPSCs from bovine mesenchymal stem cells (bMSCs) by overexpression of lysine-specific d...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-10, Vol.22 (19), p.10489
Main Authors: Su, Yue, Wang, Ling, Fan, Zhiqiang, Liu, Ying, Zhu, Jiaqi, Kaback, Deborah, Oudiz, Julia, Patrick, Tayler, Yee, Siu Pok, Tian, Xiuchun (Cindy), Polejaeva, Irina, Tang, Young
Format: Article
Language:English
Subjects:
Antigens
bovine
Cattle
Cell proliferation
Cell self-renewal
Cloning
Colonies
Colonization
Cytology
differentiation
Efficiency
embryo aggregation
Embryo cells
Embryos
Fibroblasts
Genetic engineering
induced pluripotent stem cells (iPSCs)
Karyotypes
Kinases
KLF4 protein
Lysine
Mesenchyme
Morphology
Nuclear transfer
Oct-4 protein
Pluripotency
reprogramming
Stem cell transplantation
Stem cells
Transcriptomes
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Summary:Pluripotent stem cells (PSCs) have been successfully developed in many species. However, the establishment of bovine-induced pluripotent stem cells (biPSCs) has been challenging. Here we report the generation of biPSCs from bovine mesenchymal stem cells (bMSCs) by overexpression of lysine-specific demethylase 4A (KDM4A) and the other reprogramming factors OCT4, SOX2, KLF4, cMYC, LIN28, and NANOG (KdOSKMLN). These biPSCs exhibited silenced transgene expression at passage 10, and had prolonged self-renewal capacity for over 70 passages. The biPSCs have flat, primed-like PSC colony morphology in combined media of knockout serum replacement (KSR) and mTeSR, but switched to dome-shaped, naïve-like PSC colony morphology in mTeSR medium and 2i/LIF with single cell colonization capacity. These cells have comparable proliferation rate to the reported primed- or naïve-state human PSCs, with three-germ layer differentiation capacity and normal karyotype. Transcriptome analysis revealed a high similarity of biPSCs to reported bovine embryonic stem cells (ESCs) and embryos. The naïve-like biPSCs can be incorporated into mouse embryos, with the extended capacity of integration into extra-embryonic tissues. Finally, at least 24.5% cloning efficiency could be obtained in nuclear transfer (NT) experiment using late passage biPSCs as nuclear donors. Our report represents a significant advance in the establishment of bovine PSCs.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms221910489