Final Report Summary - MANISTEC (Manipulating and Imaging Stem Cells at Work)
Stem cells are promise and threat at the same time. To understand how stem cells act it is crucial to study their behaviour in their natural context. Following and manipulating an individual stem cell and its descendants on their path to differentiation has so far not been possible. We have combined novel genetic tools to label and manipulate individual stem cells with advanced 4D imaging to address stem cell behaviour and factors governing it in the context of the retinal stem cell niche in the fish medaka (Oryzias latipes).
Stings of cell representing clones originating from one single wild type or manipulated cell were followed in their natural context. This allowed directly measuring the physiological consequences of the precise manipulations introduced. One of the striking findings our four wok was that stem cells not only contribute to the growth and regeneration of the eye but unexpectedly are key for establishing and maintaining its shape. The growing retina does not require any additional shaping elements since the shape is programmed in the behaviour of stem cells. Their division-rate and direction is the crucial component. We found this by developing a virtual retina, a computer model which was integrating our data. This allowed running experiments in the computer and developing and pre-validating hypotheses in the model. Eventually we could validate those hypotheses in few selected experiments using the precise tools we had established for functionally addressing individual cells in their natural context.
A global conclusion from our work is a shift of paradigms in biology. Visualisation of molecular processes in the context of the organism is the new biology, and we for sure are not the only lab contributing to that. “Seeing is believing” is the anchor point in this new biology, even in long term processes. Our work has shown that the visualisation of acute decision making processes of individual cells in their natural or altered (diseased, etc) context ultimately uncovers the role of the partners addressed.
Stings of cell representing clones originating from one single wild type or manipulated cell were followed in their natural context. This allowed directly measuring the physiological consequences of the precise manipulations introduced. One of the striking findings our four wok was that stem cells not only contribute to the growth and regeneration of the eye but unexpectedly are key for establishing and maintaining its shape. The growing retina does not require any additional shaping elements since the shape is programmed in the behaviour of stem cells. Their division-rate and direction is the crucial component. We found this by developing a virtual retina, a computer model which was integrating our data. This allowed running experiments in the computer and developing and pre-validating hypotheses in the model. Eventually we could validate those hypotheses in few selected experiments using the precise tools we had established for functionally addressing individual cells in their natural context.
A global conclusion from our work is a shift of paradigms in biology. Visualisation of molecular processes in the context of the organism is the new biology, and we for sure are not the only lab contributing to that. “Seeing is believing” is the anchor point in this new biology, even in long term processes. Our work has shown that the visualisation of acute decision making processes of individual cells in their natural or altered (diseased, etc) context ultimately uncovers the role of the partners addressed.