For the first time, researchers using laboratory techniques alone and no animal hosts have isolated sex-cell precursors from mouse embryos, coaxed the cells into a sperm-like form, used them to fertilize mouse eggs, and ultimately formed earlystage embryos.
The research may offer a breakthrough tool for studies of embryonic cells and gene delivery, potentially helping scientists develop treatments for infertility and providing insight into the growth of certain tumors.
The researchers, led by George Daley of Childrens Hospital and the Dana Farber Cancer Institute in Boston and Niels Geijsen of Massachusetts General Hospital, also in Boston, report their findings in the December 10, 2003 Nature (online).
Researchers are excited about stem cells because they can be coaxed into forming a number of tissues, from bone to lung, while mature cells are limited to their given role.
The study builds upon nearly a decade of research at the Whitehead Institute for Biomedical Research, Harvard University, and the National Science Foundation (NSF) Biotechnology Process Engineering Center (BPEC) at the Massachusetts Institute of Technology (MIT), all in Cambridge, Mass., and most recently at Childrens Hospital Boston, the Dana Farber Cancer Institute and Massachusetts General Hospital.
Geijsen, Daley and their colleagues began their process by culturing mouse embryonic stem cells to form globular cell clusters called embryoid bodies.
In these embryoid bodies, cells differentiated into primordial germ cells (sex cell precursors), which the researchers were able to tag with a fluorescent chemical. The tag enabled the team to isolate and track the individual germ cells as the embryoid body developed.
Once the researchers had identified and isolated the germ cells, they were able to sustain continuous cell lines in a laboratory.
The researchers also found that embryoid bodies that were allowed to grow contained cells that differentiated into mature, male, sex cells similar to sperm, but they lacked tails. The team isolated those cells and injected them directly into mouse egg cells.
The eggs essentially became fertilized, and an entirely new line of early-stage mouse embryos began to grow.
In September, a team led by Toshiaki Noce of Mitsubishi Kagaku Institute of Life Sciences in Japan reported that they had derived sperm cells from embryonic stem cells. However, Gejsen, Daley and their colleagues are the first to complete the process through to the embryo stage using only laboratory techniques.
"The big difference is that our work was entirely done in vitro," says Geijsen, "whereas Noces group transplanted the primordial germ cells back into mouse testes to let the sperm develop."
Both approaches offer unique advantages, with the earlier study yielding mature sperm with tails, and the recent study providing the flexibility of in vitro ("in glass," or outside of an animal) experimentation that may lead to more controlled studies.
Geijsen and his colleagues also found that while many primordial germ cells formed in the laboratory environment during their study, only a few developed further into the sperm precursor cells.
"We want to understand what is missing, what we would need to make more germ cells," says Geijsen. "This understanding might have applications for treatment of male infertility," he added, for the condition can be caused by a failure of sperm to fully mature within the testicles.
The researchers also hope to use the germ cell lines to study "imprints," genetic instructions that regulate certain genes yet are missing from embryonic germ cells.
"The erasure of imprints in the primordial germ cells could have implications in cancer research," says Geijsen. "In certain tumors, imprints are erased, leading to over- expression of the imprinted gene. Since many imprinted genes have a function in controlling cell proliferation, this loss of imprinting can cause the cell to grow out of control," Geijsen added.
If the researchers can determine what causes the loss of imprints in embryonic germ cells, they can attempt to find, and counter, the mechanism that is erasing imprints in cancer cells.
The findings also contribute detailed knowledge regarding the general development of stem cells, some of the workhorses of gene therapy research and a principal target of study at NSFs BPEC where Daley also serves as a researcher.
"Daley and his colleagues provide medical and biological expertise to BPEC, and in collaboration with other life science and engineering experts at the center, they conduct the basic research necessary for a complete understanding of stem cells," says Sohi Rastegar, the NSF program director who oversees the agencys support of BPEC and several other bioengineering centers.
"To develop effective gene therapy for difficult diseases such as sickle cell anemia and muscular dystrophy, the use of embryonic stem cells is one of the most promising approaches and to that end fundamental knowledge of stem cells is a prerequisite," says Rastegar.
In addition to NSF, this research was also supported by the National Institutes of Health, the Dutch Cancer Society, the Leukemia and Lymphoma Society and the Harvard Society of Fellows.
Josh Chamot | National Science Foundation
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy