Pluripotent stem cells
Pluripotent stem cells (PSCs) are the unicellular equivalent to whole animals, capable of giving rise to all adult cell types, including the gametes. PSCs are either derived from preimplantation embryos (ePSCs, also called embryonic stem cells; ESCs) or from delivering pluripotency-inducing genes into somatic cells (induced pluripotent stem cells or iPSCs). The generation of naïve PSCs depends on efficient nuclear reprogramming, the process that instructs specialised cells to re-acquire authentic pluripotency. Dr. Oback’s team focuses on epigenetic reprogramming into pluripotency in livestock.
Our goal, which we have pursued for more than a decade, is to reprogram cells of high genetic value into animals. By increasing the efficiency of this process, we aim to accelerate genetic gain and benefit animal breeding.
We are using two main approaches.
First, we are working on understanding and improving reprogramming during nuclear transfer (NT) cloning. This entails i) engineering new devices to automate high-throughput NT cloning, and ii) manipulating the reprogrammability of NT donor cells as well as the reprogramming ability of NT recipient oocytes. Specifically, we have focused on finding structural correlates for altered reprogramming function in the chromatin organization of donor and recipient cells.
Second, and more recently, we are devising new strategies to efficiently convert livestock embryos into ePSCs and then ePSC-derived animals. This includes i) developing single nucleotide polymorphism (SNP) chip- and DNA sequencing-based genome-wide selection methods to reliably pick bovine embryos with outstanding genotypes from embryo biopsies, ii) efficiently derive ePSCs from high-value embryos, and iii) evaluate genomically selected ePSCs using molecular and functional pluripotency assays, including their ability to form fertile animals.