Dr. Wu’s main research interests are focused on thegeneration of new pluripotent stem cells (PSCs) for gaining novel insights in basic biology and developing new translational applications, as well as developing novel and efficient genome and epi-genome editing tools.He has expanded the spectrum of pluripotent states by capturing novel pluripotent stem cells with distinct molecular and phenotypic featuresand derived novel PSCs from several rodent, livestock and primate species. Dr. Wu has also helped develop a robust homology-independent targeted integration (HITI) strategy that allows for efficient DNA knock-in in both dividing and non-dividing cells in vitro and in vivo, and a stable and wide range DNA methylation method based on targeted insertion of CpG free sequence in CpG islands in pluripotent stem cells (PSCs). Moreover, together with his collaborators, Dr. Wu helped devise effective strategies to safely repair disease-causing mitochondria and nuclear DNA mutations in one-cell human embryos. More recently, Dr. Wu has succeeded in generating PSC-derived interspecies chimeras and developed an efficient and versatile interspecies blastocyst complementation system for organ generation, which bodes hope for solving the severe worldwide shortage of donor organs.
Efficient derivation of pluripotent stem cells from livestock species
1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Pluripotent stem cells (PSCs) can be derived from pre-implantation embryos (embryonic stem cells, ESCs), or obtained through reprogramming somatic cells with pluripotency factors (induced pluripotent stem cells, iPSCs)1. From agricultural and biomedical perspectives, the generation of stable PSCs from livestock species is important for genomic testing and selection, genome engineering, and modeling human diseases. The recent advancements in genome editing, e.g. CRISPR/Cas9, have facilitated the introduction of complex genomic modifications, which combined with somatic cell nuclear transfer (SCNT), represents a powerful platform for the generation of transgenic livestock species with desirable traits. Until now, however, stable PSC lines from common livestock species including cattle, sheep and horse have been difficult to derive and maintain, and PSCs analogous to those described for rodents and primates have not been produced. Taking advantage of several novel culture conditions developed in our lab2-4, we have succeeded in the derivation of stable ESCs from both cattle5 and sheep blastocysts, as well as iPSCs from horse fibroblasts. These advances open the possibility for genomic selection, genome editing, and production of livestock species with high genetic value.
1. Wu, J. & Izpisua Belmonte, J. C. Dynamic Pluripotent Stem Cell States and Their Applications. Cell Stem Cell 17, 509–525 (2015).
2. Wu, J. et al. An alternative pluripotent state confers interspecies chimaeric competency. Nature 521, 316–321 (2015).
3. Wu, J. et al. Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell 168, 473–486.e15 (2017).
4. Yang, Y. et al. Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency. Cell 169, 243–257.e25 (2017).
5. Bogliotti, Y. S. et al. Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts. Proc. Natl. Acad. Sci. U.S.A. 115, 201716161–2095 (2018).