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
Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences
Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences