Department of Cell and Developmental Biology
Yet they do transform themselves…
As recently as a few years ago, everything seemed so clear: With the birth of a human being, the organism reaches a point of no return. Whether it’d be a skin, hair, fat or blood cell, no differentiated cell in the body – so one thought – can ever become different from what it is.
But this dogma has been toppled from its pedestal. Initial studies have shown that mature body cells can, in fact, be transformed into jacks-of-all-trades, similar to embryonic stem cells. Like the latter, the reprogrammed cells have a fascinating capability called pluripotency: They are able to transform themselves into more than 200 types of body cells. Much hope has been placed in these cells, as it may be possible to treat incurable diseases, such as Parkinson’s or diabetes, using the patient’s own healthy replacement cells.
But, how does pluripotency develop and what are the mechanisms that drive this process? Hans Schöler and his team have made good progress in answering this question. The researchers have shown that a gene called Oct4 plays a key role. Normally, it is only expressed in two types of cells, which are completely undeveloped: embryonic stem cells and precursors of egg and sperm cells (gametes). By contrast, in all mature cells, Oct4 is in a Sleeping Beauty−like state. If we want to transform mature cells into pluripotent cells, Oct4 must be targeted and activated.
Today, we already have several techniques at our disposal. However, until now none has proved optimal. MPI researchers are therefore striving to develop methods with which the reprogramming of Oct4 (and any other required genes) can take place in a more targeted way and with as few adverse effects as possible for the patient.
Benefits to society
The process driving a cell's journey from totipotency to tissue-resident specialist lies at the heart of how we become complex multicellular living organisms. If we can understand and decipher the processes involved in creating, maintaining, and controlling pluripotency and differentiation, we open up a realm of possibilities:
- With reprogramming available as a standard tool to generate pluripotent cells from anyone, in the long term we have a potentially limitless source for forming individualized replacement parts for our bodies.
- The ability to turn anyone's skin cells into stem cells means we can generate disease models for conditions with a high scarcity of donor tissues, such a neurodegenerative diseases. By creating stem cells from patients which in turn can become neurons, we can test thousands of potential new drugs on the very cells that become diseased in patients's brains without having to worry about cell sourcing.
- By understanding how cells can be induced to become pluripotent again, we can develop new ways to turn cells into multipotent precursors within their respective tissues and organs. These new local stem cells can repair damage locally by replacing lost tissues.