Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Biologists Reprogram Skin Cells to Mimic Rare Disease


Additional tool accelerates personalized medicine research

Johns Hopkins stem cell biologists have found a way to reprogram a patient’s skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia.

courtesy Cell Press

Neural crest cells were made from reprogrammed adult skin cells. A single neural crest cell divided many times and these cells (green) were coaxed to become four different types of adult cells, as shown by the presence of cell-specific proteins (red). Clockwise from upper left corner: nerve cells, smooth muscle cells, pigment-producing skin cells and cells that protect and support nerve cells.

The process requires growing the skin cells in a bath of proteins and chemical additives while turning on a gene to produce neural crest cells, which give rise to several adult cell types.

The researchers say their work substantially expedites the creation of neural crest cells from any patient with a neural crest-related disorder, a tool that lets physicians and scientists study each patient’s disorder at the cellular level.

... more about:
»Biologists »Cells »Disease »Medicine »Stem »disorders »neural »skin »stem cells

Previously, the same research team produced customized neural crest cells by first reprogramming patient skin cells into induced pluripotent stem (iPS) cells, which are similar to embryonic stem cells in their ability to become any of a broad array of cell types.

“Now we can circumvent the iPS cells step, saving seven to nine months of time and labor and producing neural crest cells that are more similar to the familial dysautonomia patients’ cells,” says Gabsang Lee, Ph.D., an assistant professor of neurology at the Institute for Cell Engineering and the study’s senior author. A summary of the study will be published online in the journal Cell Stem Cell on Aug. 21.

Neural crest cells appear early in human and other animal prenatal development, and they give rise to many important structures, including most of the nervous system (apart from the brain and spinal cord), the bones of the skull and jaws, and pigment-producing skin cells.

Dysfunctional neural crest cells cause familial dysautonomia, which is incurable and can affect nerves’ ability to regulate emotions, blood pressure and bowel movements. Less than 500 patients worldwide suffer from familial dysautonomia, but dysfunctional neural crest cells can cause other disorders, such as facial malformations and an inability to feel pain.

The challenge for scientists has been the fact that by the time a person is born, very few neural crest cells remain, making it hard to study how they cause the various disorders.

To make patient-specific neural crest cells, the team began with laboratory-grown skin cells that had been genetically modified to respond to the presence of the chemical doxycycline by glowing green and turning on the gene Sox10, which guides cells toward maturation as a neural crest cell.

Testing various combinations of molecular signals and watching for telltale green cells, the team found a regimen that turned 2 percent of the cells green. That combination involved turning on Sox10 while growing the cells on a layer of two different proteins and giving them three chemical additives to “rewind” their genetic memory and stimulate a protein network important for development.

Analyzing the green cells at the single cell level, the researchers found that they showed gene activity similar to that of other neural crest cells. Moreover, they discovered that 40 percent were “quad-potent,” or able to become the four cell types typically derived from neural crest cells, while 35 percent were “tri-potent” and could become three of the four. The cells also migrated to the appropriate locations in chick embryos when implanted early in development.

The team then applied a modified version of the technique to skin cells from healthy adults and found that the skin cells became neural crests at a rate similar to the team’s previous experiments.

Finally, the investigators used their regimen on skin cells from patients with familial dysautonomia, then compared these familial dysautonomia-neural crest cells to the control neural crest cells made from healthy adults. They identified 412 genes with lower activity levels in the familial dysautonomia-neural crest cells, of which 98 are involved in processing RNA products made from active genes.

According to the authors, this new observation offers insight into what goes wrong in familial dysautonomia.

“It seems as though the neural crest cells created directly from patient skin cells show more of the characteristics of familial dysautonomia than the neural crest cells we created previously from induced pluripotent stem cells,” says Lee. “That means they should be better predictors of what happens in a particular familial dysautonomia patient, and whether or not a potential treatment will work for any given individual.”

The method they devised should also be applicable to skin cells taken from people with any of the other diseases that result from dysfunctional neural crest cells, such as congenital pain disorders and Charcot-Marie-Tooth diseases, Lee says.

Other authors of the report include Yong Jun Kim, HoTae Lim, Zhe Li, Yohan Oh, Irina Kovlyagina, InYoung Choi and Xinzhong Dong of the Johns Hopkins University School of Medicine.

This work was supported by grants from the New York Stem Cell Foundation (Robertson Investigator Award) and the Maryland Stem Cell Research Fund (TEDCO).

On the Web:

Link to article (live after embargo lifts):

Lee Profile

Contact Information

Catherine Kolf
Senior Communications Specialist
Phone: 443-287-2251
Mobile: 443-440-1929

Catherine Kolf | newswise

Further reports about: Biologists Cells Disease Medicine Stem disorders neural skin stem cells

More articles from Life Sciences:

nachricht High-arctic butterflies shrink with rising temperatures
07.10.2015 | Aarhus University

nachricht Long-term contraception in a single shot
07.10.2015 | California Institute of Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Kick-off for a new era of precision astronomy

The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.

As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...

Im Focus: Locusts at the wheel: University of Graz investigates collision detector inspired by insect eyes

Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.

Inspired by insects

Im Focus: Physicists shrink particle accelerator

Prototype demonstrates feasibility of building terahertz accelerators

An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...

Im Focus: Simple detection of magnetic skyrmions

New physical effect: researchers discover a change of electrical resistance in magnetic whirls

At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...

Im Focus: High-speed march through a layer of graphene

In cooperation with the Center for Nano-Optics of Georgia State University in Atlanta (USA), scientists of the Laboratory for Attosecond Physics of the Max Planck Institute of Quantum Optics and the Ludwig-Maximilians-Universität have made simulations of the processes that happen when a layer of carbon atoms is irradiated with strong laser light.

Electrons hit by strong laser pulses change their location on ultrashort timescales, i.e. within a couple of attoseconds (1 as = 10 to the minus 18 sec). In...

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

NASA provides an infrared look at Hurricane Joaquin over time

08.10.2015 | Earth Sciences

Theoretical computer science provides answers to data privacy problem

08.10.2015 | Information Technology

Stellar desk in wave-like motion

08.10.2015 | Physics and Astronomy

More VideoLinks >>>