School of Medicine Publications and Presentations
Document Type
Article
Publication Date
10-20-2022
Abstract
Marsupials have been a powerful comparative model to understand mammalian biology. However, because of the unique characteristics of their embryology, marsupial pluripotency architecture remains to be fully understood, and nobody has succeeded in developing embryonic stem cells (ESCs) from any marsupial species. We have developed an integration-free iPSC reprogramming method and established validated iPSCs from two inbred strains of a marsupial, Monodelphis domestica. The monoiPSCs showed a significant (6181 DE-genes) and highly uniform (r2 [95% CI] = 0.973 ± 0.007) resetting of the cellular transcriptome and were similar to eutherian ESCs and iPSCs in their overall transcriptomic profiles. However, monoiPSCs showed unique regulatory architecture of the core pluripotency transcription factors and were more like marsupial epiblasts. Our results suggest that POU5F1 and the splice-variant-specific expression of POU5F3 synergistically regulate the opossum pluripotency gene network. It is plausible that POU5F1, POU5F3 splice variant XM_016427856.1, and SOX2 form a self-regulatory network. NANOG expression, however, was specific to monoiPSCs and epiblasts. Furthermore, POU5F1 was highly expressed in trophectoderm cells, whereas all other pluripotency transcription factors were significantly downregulated, suggesting that the regulatory architecture of core pluripotency genes of marsupials may be distinct from that of eutherians.
Recommended Citation
Kumar, S., De Leon, E. M., Granados, J., Whitworth, D. J., & VandeBerg, J. L. (2022). Monodelphis domestica Induced Pluripotent Stem Cells Reveal Metatherian Pluripotency Architecture. International journal of molecular sciences, 23(20), 12623. https://doi.org/10.3390/ijms232012623
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
International journal of molecular sciences
DOI
10.3390/ijms232012623
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
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