The main role of mature Sertoli cells is to provide support and nutrition to the developing sperm cells. Furthermore, Sertoli cells have been demonstrated to possess trophic properties, which have been utilized for the protection of non-testicular cellular grafts in transplantations.
However, mature Sertoli cells are mitotically inactive, and the primary immature Sertoli cells during prolonged cultures degenerate in the petri dish. Therefore, finding an alternative source of these cells independent of the donor testis cells is of paramount interest both for basic research and clinical applications.
“The idea is if you could make Sertoli cells from a skin cell, they’d be accessible for supporting the spermatogenesis process when conducting in vitro fertilization assays or protecting other cell types such as neurons when co-transplanted in vivo,” says Whitehead Institute Founding Member Rudolf Jaenisch. “Otherwise, you could get proliferating cells only from fetal testis.”
Jaenisch lab researchers have seemingly overcome the supply and lifespan challenges through trans-differentiation, the process of reprogramming a cell directly from one mature cell type to another without first taking the cell in question all the way back to the embryonic stem-cell stage. Unlike other reprogramming methods that produce induced pluripotent stem cells (iPSCs), trans-differentiation does not rely on the use of genes that can cause cancer.
As reported in Cell Stem Cell’s September issue, scientists trans-differentiated mouse skin cells into embryonic Sertoli-like cells by breaking the process into two main steps, mimicking Sertoli cells’ development in the testis. The first step in this progression transformed the skin fibroblasts from their mesenchymal state to a sheet-like epithelial state. In the second step the cells acquired the capability to attract each other to form aggregates as seen in vivo between embryonic Sertoli cells and germ cells.
Next the scientists devised a cocktail of five transcription factors that activate the epithelial cells’ embryonic Sertoli cell genetic program. The resulting cells exhibited many of the characteristics of embryonic Sertoli cells, including aggregating, forming tubular structures similar to the seminiferous tubules found in the testis, and secreting the typical Sertoli cell factors. When injected into a mouse fetal testis, the trans-differentiated cells migrated to the proper place and integrated into the endogenous tubules. Overall, the injected cells behaved like endogenous embryonic Sertoli cells, despite expressing a few genes differently.
“The injected trans-differentiated cells were closely interacting with the native germ cells, which shows that they definitely do not have any bad effect on the germ cells,” says Yossi Buganim, a postdoctoral researcher in the Jaenisch lab and first author of the Cell Stem Cell paper. “Instead, they enable those germ cells to survive.”
In fact, when the embryonic Sertoli-like cells were used to sustain other cells in a Petri dish, Buganim noted that the cells supported by the trans-differentiated cells thrived, living longer than cells sustained by actual native Sertoli cells.
Encouraged by these results in vitro, Buganim says he would like to investigate whether the embryonic Sertoli-like cells retain this enhanced supportive capacity after transplantation into the brain, where the cells could sustain ailing neurons. If so, they could have applications in the development of neuron-based therapies for neurodegenerative disorders such as ALS and Parkinson’s disease.
This work was supported by the National Institutes of Health (NIH) grants R37-CA084198 and RO1-HD045022, and the Howard Hughes Medical Institute (HHMI).
Written by Nicole Giese Rura
Rudolf Jaenisch's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.
“Direct reprogramming of fibroblasts into embryonic Sertoli-like cells by defined factors”
Yosef Buganim (1), Elena Itskovich (1), Yueh-Chiang Hu (1,3), Albert W. Cheng (1,2), Kibibi Ganz (1), Sovan Sarkar (1), Dongdong Fu (1), Grant Welstead (1), David C. Page (1,2,3), and Rudolf Jaenisch (1,2).
Cell Stem Cell, September 7, 2012 print issue.1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
3. Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA
Nicole Giese Rura | EurekAlert!
Further reports about: > Biomedical > Buganim > Cell-Supporting > Embryonic > Medical Wellness > Sertoli > Sertoli-Like > Whitehead > cell death > cell type > clinical application > germ > germ cells > information technology > methanol fuel cells > neurodegenerative disorder > skin > transcription factor
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Earth Sciences
19.07.2018 | Power and Electrical Engineering
19.07.2018 | Materials Sciences