Working on daily basis with pluripotent stem cells cultured in 3D in epiblast conformation, developmental biologist Marta Shahbazi, group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK, explains how 3D organization affects either the maintenance of pluripotency or triggers cell differentiation, and the importance of this research for therapeutic applications.
Transcript:
So, we’ve generated a new 3D culture system in the lab, So we basically maintain pluripotency and self-renewal in 3D as epithelial spheroids let’s say but in our system there is a certain degree of heterogeneity, so some cells are differentiating in the culture. And those are actually the cells that are losing their organization. So, we are interested in this heterogeneity, not so much related maybe to cell-cell communication but how cell variability arises within a homogeneous culture, right? And what is the role of cellular organization there So these are questions that we are trying to address at the moment. Yeah, the rupture of symmetry is a big thing in early development, and you go from something that is sort of homogeneous into something that is organized. And even, I mean, in invertebrate world you have lot’s of -and also in vertebrate world I would say, but at least in non-mammalian world- you have lot’s of polarization that are already there. Even at the onset of development, it is not exactly the case in the mammalian development. So I guess that’s a very important part of what you do. Yeah, and we think the system we have is quite usefull to address that question, because the signaling environment is exactly the same, the factors in the media are the same, and yet in some of the structures some cells manage to escape and differentiate. And also actually the cells that are losing their normal epithelial organization. So we think the two things are actually linked. So do you think that this growing understanding of the … I’d call it “micro-meso scale”, I don’t know how to call that… Like the ‘topology’ and the organization of cells at the early stages of the embryo and even going forward into adulthood is something that, I would say therapeutic initiatives are attuned to
Or it’s something that is really a lab thing, that will transition much further down the line into what people are trying to do in therapeutic fields No, I think the kind of research we are doing is very very relevant for like a clinical setting, right? Because, I mean, is influencing how cells differentiate and the level of heterogeneity and cell-cell variability This is extremely important when you are trying to differentiate pluripotent cells in vitro to generate either tissues or cells types.
Understanding what is the role of that cell-cell variability And even heterogeneity across lines as well, right? So this is one of the, let’s call it bottlenecks maybe on like human embryonic stem cell research and stem cell differenciation. How different lines are extremely different, behaving different ways, with a lot of heterogeneity, so how do you control all of that ? So I think there are still unresolved questions that require much more basic research.