By subjecting skin cells to a specific combination of cell programming molecules, researchers managed to transform them into brain cells that act like native cells.
The research is uncommon because, unlike many cell transformation techniques, the cells did not come back to a stem cell stage first – they transformed directly into brain cells – thus preventing the risk of developing many other kinds of cells.
And the research is unique, because the team managed to reprogram the skin cells to turn into a specific kind of brain cell rather than a range of brain cells.
Publishing in the journal Neuron, scientists from Washington University School of Medicine, report how they applied a specific combination of microRNAs and transcription aspects to reprogram the skin cells into a specific kind of brain cell recognized as medium spiny neurons.
The medium spiny neurons they created – which survived for at least 6 months after injection into the brains of mice – are essential for managing movement and are the primary type impacted in Huntington’s disease.
Huntington’s disease is an inherited genetic condition that leads to involuntary movements and steady decline of mental capability. Sufferers with the condition – which generally starts in middle age – can survive for 20 years following symptoms start, even though these progressively get more serious.
Transformed cells demonstrated properties of native cells
Senior author Dr. Andrew S. Yoo, states that not only did the new cells survive in the mouse brain, but they also demonstrated qualities identical to native cells:
“These cells are identified to increase projections into specific brain areas. And we identified the human transplanted cells also linked to these distant objectives in the mouse brain. That’s a milestone point about this paper.”
Due to the fact they used adult human skin cells in the research – and not mouse cells or human cells at an earlier stage of progression – the research team believes the work reveals the possible for using sufferers’ own cells in regenerative treatment. This is essential because treatments can use readily accessible cells and also prevent the issue of immune rejection.
For their research, Dr. Yoo and co-workers cultured the skin cells in an atmosphere that imitates that of brain cells. In earlier work, they had already found that subjecting skin cells to two small RNA molecules known as miR-9 and miR-124 can turn them into various types of brain cell.
Even though they are even now attempting to work out exactly what happens, the team considers the two small RNA molecules open up the firmly packed DNA within cells that keeps instructions for making brain cells, enabling the genes specific to their development and function to be switched on.
Having shown that visibility to these small RNA molecules transforms skin cells into a mix of brain cells, the research team started fine-tuning the chemical signals. They did this by including molecules known as transcription elements that they already knew existed in the portion of the brain where medium spiny neurons are abundant.
Transcription aspects guide the cells to turn out to be a specific type
Co-first author Matheus B. Victor, says they believe that the small RNA molecules are “doing the heavy lifting,” and:
“They are priming the skin cells to turn out to be neurons. The transcription aspects we add then guide the skin cells to turn out to be a particular subtype, in these situation medium spiny neurons. We believe we could generate various forms of neurons by switching out various transcription factors.”
The group also revealed that when the skin cells are revealed to the transcription aspects alone, devoid of the small RNA molecules, the skin cells do not alter successfully.
The research team also taken out comprehensive tests to show the new brain cells had the outline of native medium spiny neurons. They indicated the suitable genes for their particular type and did not show genes for other kinds of neurons.
And, when replanted into the brains of mice, the transformed cells viewed like native medium spiny neurons and behaved like them.
The research team is now utilizing skin cells from sufferers with Huntington’s condition and transforming them into medium spiny neurons using their new method. They also prepare to inject the cells into mice with the disease.