Using human stem cells, researchers have created precursors to egg and sperm -- called primordial germ cells -- in a petri dish. Until this work, published in Cell today, the feat has only been achieved using rodent stem cells.
One of the first events in the early development of both mice and men is the creation of primordial germ cells (PGCs). After an egg is fertilized by sperm, embryonic stem cells begin to differentiate into various basic cell types that make up the fetus. A small number of these stem cells develop into primordial germ cells, which will go on to become egg or sperm. "Germ cells are 'immortal' in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next," Cambridge’s Azim Surani says in a university statement.
Within the last decade, researchers have been "reprogramming" adult cells (such as skin cells) to act like embryonic stem cells with the potential to differentiate into practically any type of cell in the body. These induced pluripotent stem (iPS) cells have been used to develop human retinas and intestines, for example. Researchers have also created iPS cells that could differentiate into primordial germ cells, but it’s only been successful in rodents.
Now, a team of researchers from the U.K. and Israel traced the genetic chain of events that directs a human stem cell to develop into a primordial germ cell. This stage in our development is called "specification," and once PGCs become "specified," they continue developing toward precursor sperm cells or ova “pretty much on autopilot,” Jacob Hanna from the Weizmann Institute of Science says in a news relesae.
They found that a master gene called SOX17 helps direct the stem cells in this process. Previous work found that SOX17 was involved in directing stem cells to become endodermal cells -- which develop into lung, gut, and pancreas cells -- but this is the first time it’s been seen in primordial germ cell specification. (Surprisingly, the mouse equivalent of this gene is not involved in this process for them.)
The international team followed their discovery by actually making primordial germ cells in the lab. Using both embryonic stem cells and iPS cells (reprogrammed adult skin cells) from both males and females, the researchers made sex cell precursors with up to 40 percent efficiency. When they compared the protein markers of their new, lab-grown PGCs with real PGCs collected from aborted fetuses, Nature reports, they were found to be very similar.
Pictured below are clusters of human embryonic stem cells that were differentiated to an early germ cell state (shown as colored cells). Each color reveals the expression of a different gene for PGCs, so researchers could gauge how many of the cells had been programed. All three are combined in a single image on the right.
Images: Walfred Tang, University of Cambridge (top), Weizmann Institute of Science (middle)