Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Create Germ Cell-Supporting Embryonic Sertoli-Like Cells From Skin Cells

10.09.2012
Using a stepwise trans-differentiation process, Whitehead Institute researchers have turned skin cells into embryonic Sertoli-like cells.

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.

Full Citation:

“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
2. Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, Cambridge, MA 02139, USA

3. Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA

Nicole Giese Rura | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>