The first early human eggs from stem cells

Conception’s mission is to turn stem cells into human eggs and redefine fertility. We want to share an exciting update that we have generated the first early human egg cells (‘primary oocytes’) derived from stem cells. After performing a simple blood draw, we converted blood cells into stem cells, and then coaxed those stem cells into becoming miniature human ovaries that contain the early eggs. While there is still work ahead to grow these eggs to full maturity, we think this is a major scientific advance. Conception’s mission is to turn stem cells into human eggs and redefine fertility. We want to share an exciting update that we have generated the first early human egg cells (‘primary oocytes’) derived from stem cells. After performing a simple blood draw, we converted blood cells into stem cells, and then coaxed those stem cells into becoming miniature human ovaries that contain the early eggs. While there is still work ahead to grow these eggs to full maturity, we think this is a major scientific advance. Making viable eggs from stem cells has already been accomplished in mice. In 2016, our collaborator Katsuhiko Hayashi demonstrated that mouse skin cells can be turned into ‘induced pluripotent stem cells’ (iPSCs, which are engineered cells capable of becoming any kind of cell in the body) and then turned into usable eggs. These eggs produced healthy pups that lived normal lifespans and reproduced naturally, having healthy pups of their own. This process, known as "in vitro gametogenesis” (IVG), has been far easier to achieve in mice than in larger animals. Still, given how dramatically impactful this technology could be, it is well worth pursuing for human application. IVG has the potential to redefine reproduction worldwide. From a simple blood draw, one could make as many healthy eggs as a family needs. This capability could create freedom from biological and genetic limits. It could dramatically expand families’ options for having healthy children and enable women to have children at a much older age– all without the hormone injections or surgical retrieval currently required for IVF. The technology is one of the most complex therapies ever to be developed. We are not making just a single cell type; we are building entire mini-ovaries in the lab derived from stem cells, as the whole organ is important for proper egg development. We’re excited that we’ve made hugely significant progress towards this goal, and we wanted to share a peek into our process. Conception's thesis is simple: there are no useful shortcuts. A cell that expresses a few egg markers is not enough. We need to rebuild, as closely as possible, the sequence that nature uses — and benchmark our cells against human development at every major step. Our approach follows the major steps of egg development above in Figure 3. After taking a blood sample, we turn a subset of blood cells into iPSCs, and then guide the iPSCs toward becoming each of the kinds of cells found in a developing ovary: ‘primordial germ cells’ are the cells that will eventually become eggs, and ‘ovarian helper cells’ are the supporting players that provide essential signals for the eggs. Together, these cells form ‘mini-ovaries,’ small 3-dimensional “balls of cells” that mimic a true human ovary. Below on the left, you can see what our mini-ovaries look like with the naked eye. The middle image shows thin slices of those same mini-ovaries on a microscope slide; each white circle is one slice of a mini-ovary. These slides are then used for our image analysis on the right where we stain the mini-ovaries with cell and stage-specific dyes to understand how they are developing. In our research, we generate thousands of mini-ovaries, containing millions of future egg cells, to study, improve, and benchmark their development in parallel. Inside the mini-ovaries, primordial germ cells are surrounded by the ovarian helper cells they need to begin moving through the next three stages of egg development: 1) The primordial germ cells progress toward ‘oogonia’ 2) The oogonia enter into meiosis, the special cell division needed to make eggs 3) As they become early egg cells, they form follicles, the essential ovarian units that house each egg Along the way, we rigorously benchmark cell identity against a massive internally-assembled reference atlas of human ovary molecular data. This atlas includes millions of datapoints spanning a wealth of sequenced features capturing many layers of cell biology. Comparisons to this atlas (including with proprietary deep learning models) allow us to confidently chart our path forward biologically, while confirming the fidelity of our protocol and thus the quality of our cells. One of the most important measures of success for us is function - can these cells faithfully perform the same roles of cells in a real ovary? We’ll walk through how we benchmark that in each step below. An early sign of success for our mini-ovaries is

The first early human eggs from stem cells

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