Differentiating human pluripotent stem cells (blue) turning into human germ cells (pink and white). Image: UCLA Broad Stem Cell Research Center/Cell Reports
Research into how and when the precursors to eggs and sperm are formed during development could help pave the way for generating egg and sperm cells in the lab to treat infertility. The study describes the way in which human stem cells evolve into germ cells, the precursors for egg and sperm cells.
“Right now, if your body doesn’t make germ cells, then there’s no option for having a child that’s biologically related to you,” says Amander Clark, PhD, chair of the UCLA Department of Molecular, Cell and Developmental Biology and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “What we want to do is use stem cells to be able to generate germ cells outside the human body, so that this kind of infertility can be overcome.”
It is estimated that infertility affects 10 percent of the U.S. population, and infertility rates have increased over the past several decades because more people are waiting longer to have children. Many forms of infertility can be treated using procedures that join egg and sperm together outside the body, such as in vitro fertilization and intracytoplasmic sperm injection. But for people whose bodies don’t produce eggs or sperm — because of chemotherapy, radiation, genetics or other unexplained causes — those treatments aren’t an option unless a donor provides the eggs or sperm.
“With donated eggs and sperm, the child is not genetically related to one or both parents,” Dr. Clark says. “To treat patients who want a child who is genetically related, we need to understand how to make germ cells from stem cells, and then how to coax those germ cells into eggs or sperm.”
In developing male and female embryos, a subset of pluripotent stem cells — cells that have the potential to become nearly every type of cell in the body — become germ cells that later will generate eggs or sperm. Researchers previously demonstrated in a laboratory the ability to make similar stem cells, called induced pluripotent stem cells (IPS) from a person’s own skin or blood cells.
Dr. Clark and her colleagues used technology that enabled them to measure the active genes in more than 100,000 embryonic stem cells and iPS cells as they generated germ cells. Collaborators at the Massachusetts Institute of Technology developed new algorithms to analyze the massive amounts of data.
The experiments revealed a detailed timeline for when germ cells form: They first become distinct from other cells of the body between 24 and 48 hours after stem cells start differentiating into cell types that will ultimately make up all of the specialized cells in the adult body. Dr. Clark says this information can help scientists focus their efforts on that particular timeframe in future studies in order to maximize the number of germ cells they can create.
When the researchers compared the germ cells derived from embryonic stem cells with those derived from iPS cells in the lab, they found that the patterns by which genes were activated were nearly identical. “This tells us that the approach we’re using to begin the process of making germ cells is on the right track,” Dr. Clark says. “Now we’re poised to take the next step of combining these cells with ovary or testis cells.”
If the approach were to be incorporated into a future treatment for infertility, scientists might eventually be able to use a patient’s own skin cells to form stem cells that can be coaxed into both germ cells and ovarian or testis tissue — and those cell types might be able to be used to generate a person’s own eggs or sperm in the lab.
— Sarah C.P. Williams
“Human Primordial Germ Cells Are Specified,” Cell Reports, December 24, 2019
Amander Clark, PhD