Direct conversion of non-neuronal cells into nerve cells

July 02, 2018

It was already in 2012 that a team of scientists headed by Professor Benedikt Berninger first succeeded in reprogramming connective tissue cells present in the brain into neurons. Up to now, however, it was completely unknown which intermediate states these cells known as pericytes pass through in the process, and how relevant these states are for successful reprogramming. Berninger and his team have now discovered that on the way to becoming neurons pericytes need to go through a neural stem cell-like state. They succeeded in manipulating the signaling pathways in this intermediate state, which enabled them to either activate or inhibit neuronal reprogramming. The discovery may be the key to future possibilities of regenerating diseased brain tissue by directly reprogramming non-neuronal cells into neurons. The findings were recently published in Nature Neuroscience.

Pericytes regulate the diameter of small blood vessels in the brain. They are also involved in maintaining the blood-brain barrier and in wound healing. Professor Benedikt Berninger was now able to demonstrate that the targeted introduction of two proteins active in the cell nucleus, i.e., Ascl1 and Sox2, causes pericytes to assume the form and function of nerve cells. Both proteins are so-called transcription factors determining which sequences of DNA are turned on or off in a particular cell and thus the cell's form and function. When these two transcription factors are introduced into pericytes, they initiate their conversion into neurons.

"To date, however, we have been completely in the dark as to whether these cells go through distinct intermediate states during this transformation process, and how important these states are to the outcome of reprogramming," explained the lead author of the paper, Dr. Marisa Karow, a member of Berninger's team in Mainz and now a team leader at the Biomedical Center Munich at Ludwig-Maximilians-Universität München (LMU). "By analyzing the activity of genes in single cells, we were able to discover the developmental trajectory of the reprogramming process at the molecular level," added Professor Barbara Treutlein, a Max Planck team leader in Leipzig and Dresden.

The Mainz-based researchers and their cooperation partners in Saxony and Bavaria discovered that the cells must pass through a stem cell-like state during the transformation from pericyte to neuron. In the stem cell-like state, important signaling pathways are either inhibited or activated. "By manipulating these signaling pathways, we were able either to inhibit or to stimulate reprogramming to form neurons. On the one hand, this is an important piece of evidence that this state is functionally significant. On the other hand, it provides us with new ways of increasing the success of reprogramming," concluded Karow.

"We also found that, once past the stem cell-like state, the cells differentiate into two classes of neurons, i.e., excitatory and inhibitory," explained Berninger. "We hope this discovery will allow us to subsequently enhance targeted reprogramming of cells into specific neuronal subtypes." The new findings indicate it might be possible in the future to regenerate diseased brain tissue by means of the direct reprogramming of non-neuronal cells into neurons.
-end-


Johannes Gutenberg Universitaet Mainz

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.