Jump to content
RemedySpot.com

Mouse Skin Cells Turned Directly Into Neurons, Skipping IPS Stage

Rate this topic


Guest guest

Recommended Posts

http://www.medicalnewstoday.com/articles/177419.php

<http://www.medicalnewstoday.com/articles/177419.php>

[10] Mouse Skin Cells Turned Directly Into Neurons,

Skipping IPS Stage28 Jan 2010

Even Superman needed to retire to a phone booth for a quick change. But

now scientists at the Stanford University School of Medicine have

succeeded in the ultimate switch: transforming mouse skin cells in a

laboratory dish directly into functional nerve cells with the

application of just three genes. The cells make the change without first

becoming a pluripotent type of stem cell - a step long thought to be

required for cells to acquire new identities.

The finding could revolutionize the future of human stem cell therapy

and recast our understanding of how cells choose and maintain their

specialties in the body.

" We actively and directly induced one cell type to become a completely

different cell type, " said Marius Wernig, MD, assistant professor of

pathology and a member of Stanford's Institute for Stem Cell Biology and

Regenerative Medicine. " These are fully functional neurons. They can do

all the principal things that neurons in the brain do. " That includes

making connections with and signaling to other nerve cells - critical

functions if the cells are eventually to be used as therapy for

Parkinson's disease or other disorders.

Wernig is the senior author of the research, which will be published

online Jan. 27 in Nature. Graduate student Vierbuchen is the lead

author.

Although previous research has suggested that it's possible to coax

specialized cells to exhibit some properties of other cell types, this

is the first time that skin cells have been converted into fully

functional neurons in a laboratory dish. The change happened within a

week and with an efficiency of up to nearly 20 percent. The researchers

are now working to duplicate the feat with human cells.

" This study is a huge leap forward, " said Irving Weissman, MD, director

of Stanford's Institute for Stem Cell Biology and Regenerative Medicine.

" The direct reprogramming of these adult skin cells into brain cells

that can show complex, appropriate behaviors like generating electrical

currents and forming synapses establishes a new method to study normal

and disordered brain cell function. Finally we may be able to capture

and study conditions like Parkinson's or Alzheimer's or heritable mental

diseases in the laboratory dish for the first time. "

Until recently, it's been thought that cellular specialization, or

differentiation, was a one-way path: pluripotent embryonic stem cells

give rise to all the cell types in the body, but as the daughter cells

become more specialized, they also become more biologically isolated.

Like a tree trunk splitting first into branches and then into individual

leaves, the cells were believed to be consigned to one developmental

fate by physical modifications - called epigenetic changes - added to

their DNA along the way. A skin cell could no more become a nerve cell

than a single leaf could flit from branch to branch or Superman could

become Kent in midair.

That view began to change when Dolly the sheep was cloned from an adult

cell in 1997, showing that, under certain conditions, a specialized cell

could shed these restrictions and act like an embryonic stem cell.

And in 2007, researchers announced the creation of induced pluripotent

stem cells, or iPS cells, from human skin cells by infecting them with

four stem-cell-associated proteins called transcription factors. Once

the cells had achieved a pluripotent state, the researchers coaxed them

to develop into a new cell type. The process was often described in

concept as moving the skin cells backward along the differentiation

pathway (in the leaves analogy, reversing down the branch to the tree's

trunk) and then guiding them forward again along a different branch into

a new lineage.

Finally, in 2008, Doug Melton, PhD, a co-director of Harvard's Stem Cell

Institute, showed it was possible in adult mice to reprogram one type of

cell in the pancreas to become another pancreatic cell type by infecting

them with a pool of viruses expressing just three transcription factors.

As a result, Wernig, who as a postdoctoral fellow in Rudolf Jaenisch's

laboratory at the Whitehead Institute in Massachusetts participated in

the initial development of iPS cells, began to wonder whether the

pluripotent pit stop was truly necessary. Südhof, the Avram

Goldstein Professor in the Stanford School of Medicine, also

collaborated on the research.

To test the theory, Wernig, Vierbuchen and graduate student Austin

Ostermeier amassed a panel of 19 genes involved in either epigenetic

reprogramming or neural development and function. They used a virus

called a lentivirus to infect skin cells from embryonic mice with the

genes, and then monitored the cells' response. After 32 days they saw

that some of the former skin cells now looked like neural cells and

expressed neural proteins.

The researchers, which included postdoctoral scholar Zhiping Pang, PhD,

used a mix-and-match approach to winnow the original pool of 19 genes

down to just three. They also tested the procedure on skin cells from

the tails of adult mice. They found that about 20 percent of the former

skin cells transformed into neural cells in less than a week. That may

not, at first, sound like a quick change, but it is vast improvement

over iPS cells, which can take weeks. What's more, the iPS process is

very inefficient: Usually only about 1 to 2 percent of the original

cells become pluripotent.

In Wernig's experiments, the cells not only looked like neurons, they

also expressed neural proteins and even formed functional synapses with

other neurons in laboratory dish.

" We were very surprised by both the timing and the efficiency, " said

Wernig. " This is much more straightforward than going through iPS cells,

and it's likely to be a very viable alternative. " Quickly making neurons

from a specific patient may allow researchers to study particular

disease processes such as Parkinson's in a laboratory dish, or one day

to even manufacture cells for therapy.

The research suggests that the pluripotent stage, rather than being a

required touchstone for identity-shifting cells, may simply be another

possible cellular state. Wernig speculates that finding the right

combination of cell-fate-specific genes may trigger a domino effect in

the recipient cell, wiping away restrictive DNA modifications and

imprinting a new developmental fate on the genomic landscape.

" It may be hard to prove, " said Wernig, " but I no longer think that the

induction of iPS cells is a reversal of development. It's probably more

of a direct conversion like what we're seeing here, from one cell type

to another that just happens to be more embryonic-like. This tips our

ideas about epigenetic regulation upside down. "

Additional Stanford researchers involved in the study include research

assistant Yuko Kokubu.

The research was supported by Stanford's Institute for Stem Cell Biology

and Regenerative Medicine, the E. and Delia B. Baxter Foundation,

the Stinehart Jr. and the Foundation, and the National

Institutes of Health. The researchers have recently applied for a patent

on the technique.

Source: Krista Conger

Stanford University Medical Center

Article URL: http://www.medicalnewstoday.com/articles/177419.php

Main News Category: Neurology / Neuroscience

Also Appears In: Genetics, Stem Cell Research,

[10]

Link to comment
Share on other sites

Join the conversation

You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

Loading...
×
×
  • Create New...