Identity Crisis: Are we closer to understanding the requirements for cell identity?
By Nadia Rajab
The mystical world of cell development is often greeted with weary smiles. A challenging research landscape with hurdles and a continuum abyss of the unknown. The constant questioning of cell-fate decision making, discussions around the ideas of probability, all the way to the sounds of Eureka's when identifying transcription factors that promise to answer all. At what point do we put our hands up proudly and say we are still learning?
We have seen the rise and evolution of transcriptional atlases. The bringing together of data enables us to ask bigger questions and to look at the bigger picture. More data, more meaningful? The accessibility of data allows us as acommunity to harness the good work that has already been done to draw out more findings and more insight. Why make more when there is still so much to explore in what is already available? By bringing data together we have explored cell identity through a new lens. We have seen how different cells can have their very own transcriptionally-specific position on a map, and have even pondered the possibility of using their positioning to design cells that better fit into the same location. But to be assigned an identity, do they really need to share the same location or can we embrace the possibility that one cell might be capable of purchasing real estate outside the constraints of its designated address? Maybe, just maybe, cells are more complicated than we give them credit for.
When developing cells in the lab (such as from pluripotent stem cells), does mimicking development matter or does the creation of a cell that can model what you want to model a more appropriate option? To put out a more challenging question: Does development infer identity? This question is particularly exciting because it really does challenge our constrained ideas around benchmarking cells in the lab. We always see the use of generic benchmarking (proteins on a cell surface, functional assays, imaging) as the first comfort stop, but when are we going to challenge this and step outside our comfort zones? Is there beauty in identity or is there beauty in function? Why should a cell be confined to fulfilling our expectations?
When we look down the microscope, why do we need further convincing of what we already see? And how do we gain the approval of others that have their own secret suite of benchmarking requirements? Deep thinking, numerous technologies, big data…The beautiful efforts of the masses have brought us to this point. We now know cells make decisions, and we know they can go down developmental trajectories dependent on the signals (or instructions?) they receive. Transcription factors, gene expression, chromatin landscapes…what does this lead us to? Reprogramming cells it seems! Can we really force cell identity?
With increased ripples of new findings comes more curiosity and even more questions. A beautiful maze with surprises on every turn. What requirements do cells need to fulfill to be worthy of a title or annotation status? And is there anything wrong with a cell that doesn’t quite meet them?