Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Recipe for Cell Reprogramming Adds Protein

08.08.2008
Embryonic-like stem cells can be efficiently generated using a natural signaling molecule instead of the virally delivered cancer-causing gene c-Myc. The results represent progress in overcoming hurdles to the potential use of reprogrammed cells for stem-cell-based therapies in humans.

A drug-like molecule called Wnt can be substituted for the cancer gene c-Myc, one of four genes added to adult cells to reprogram them to an embryonic-stem-cell-like state, according to Whitehead researchers. Researchers hope that such embryonic stem-cell-like cells, known as induced pluripotent (IPS) cells, eventually may treat diseases such as Parkinson’s disease and diabetes.

Demonstrated in mice, the elimination of c-Myc represents an important step in creating IPS cells in a manner that in the future may be applied to human therapeutics.

“This is a good sign for the possible replacement of the other three genes used to reprogram cells,” says Ruth Foreman, a MD/PhD student in the lab of Whitehead Member Rudolf Jaenisch and a lead co-author on the paper, published online in Cell Stem Cell on August 6. The other lead co-authors are Alex Marson, an MD/PhD student in the labs of Jaenisch and Whitehead Member Richard Young, and Brett Chevalier, a research scientist in the Young lab.

... more about:
»DNA »IPS »Parkinson’s »Protein »Retrovirus »c-Myc »oncogene

“IPS cells hold great potential for future medicine, but we must learn how to generate these cells in a manner that is safe for clinical therapies,” says Young, who is also a professor of biology at Massachusetts Institute of Technology. “This advance in reprogramming is one key step toward that goal,”

Currently, IPS cells can be created by reprogramming adult cells through the use of viruses to transfer four genes (Oct4, Sox2, c-Myc and Klf4) into the cells’ DNA. The activated genes then override the adult state and convert the cells to embryonic-like IPS cells.

However, this method poses significant risks for potential use in humans.

First, the viruses employed in the process, called retroviruses, are associated with cancer because they insert DNA anywhere in a cell’s genome, thereby potentially triggering the expression of cancer-causing genes, or oncogenes. Second, c-Myc is a known oncogene whose overexpression can also cause cancer. For IPS cells to be employed to treat human diseases such as Parkinson’s, researchers must find safe alternatives to reprogramming with retroviruses and oncogenes.

Earlier research has shown that c-Myc is not strictly required for the generation of IPS cells. However, its absence makes the reprogramming process time-consuming and highly inefficient.

To bypass these obstacles, the Whitehead researchers replaced c-Myc and its retrovirus with a naturally occurring signaling molecule called Wnt3a. When added to the fluid surrounding the cells being reprogrammed, Wnt3a promotes the conversion of adult cells into IPS cells.

“We’re not sure if the Wnt molecule is doing the same thing as c-Myc or complementing c-Myc’s activity,” says Chevalier. “But it does increase stem cell growth similar to c-Myc.”

“This is a good start toward using external cues instead of genetic manipulation to reprogram cells,” says Marson. “But we still need to eliminate the need for retroviruses for the three other genes.”

Although the technique is promising in mouse cells, its potential applications in humans have not been studied, emphasizes Jaenisch, who is also a professor of biology at MIT. “Is the same pathway acting in the human system and can Wnt molecules be used to reprogram human cells?” he asks. “We don’t know, but I think those are very important questions to investigate.”

This research was supported by the National Institutes of Health.

Rudolf Jaenisch and Richard Young’s primary affiliations are with Whitehead Institute for Biomedical Research, where their laboratories are located and all their research is conducted. Jaenisch and Young are also professors of biology at Massachusetts Institute of Technology.

Full citation:
Cell Stem Cell August 7, 2008 (online August 6, 2008).
Wnt stimulation substitutes for c-Myc in reprogramming somatic cells to induced pluripotent stem cells

Alexander Marson (1,2), Ruth Foreman (1,2), Brett Chevalier (1), Michael Kahn (3,4), Richard A. Young (1,2), Rudolf Jaenisch (1,2).

1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
2. Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.
3. Institute for Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, California 90033, USA.

4. Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.

Cristin Carr | Newswise Science News
Further information:
http://www.wi.mit.edu/news/

Further reports about: DNA IPS Parkinson’s Protein Retrovirus c-Myc oncogene

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

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

Im Focus: Highly precise wiring in the Cerebral Cortex

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...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

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...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>