How do cells multi-task?
Our research interest lies in understanding the organizational principles underlying a cellular community. Similar to human society, cellular societies (organs) are required to efficiently multi-task in order to survive in an ever-changing environment. We want to understand how cells distribute the various tasks among themselves to achieve multi-tasking.
The prime reason why cells need to multi-task is that one cell cannot be optimal at all the tasks at once.
Thus, cells need to focus on a specific task, which tunes its gene expression towards the specialty. The process may be dynamic, with cells continuously shifting roles with each other. However, at a given point in time, the tradeoff in cellular responsibilities segregates a cellular community. Such tradeoffs have been suggested for cancer cells. For example, cancer cells either invest in cell division or tissue-invasion, as each of the tasks requires a specific gene regulatory network that is not compatible with each other. This tradeoff, termed ‘Go or grow’, nicely captures the requirement for adaptability, and hence diversity, for optimal survival.
In the lab, we focus on the balance between cell-cycle and function to understand how tradeoffs sculpt cellular heterogeneity. For organs with tissue-resident stem cells, the ‘division of labor’ is clear: stem cells increase the pool of differentiated cells by proliferation, while the differentiated cells perform the physiological functions of the organ. In contrast, for tissues lacking a stem cell population, the differentiated cells are responsible for undergoing cell-cycle while fulfilling the organ functions.
Organs without a bona-fide stem cell population can balance the demand for organ growth and function via two potential strategy: i) As an ‘egalitarian’ strategy, where all cells contribute equally; or ii) an ‘elitist’ strategy, where cells are specialized towards proliferative and functional capacities, generating population heterogeneity.
Using the model of two endocrine organs, the thyroid gland and pancreatic beta-cells, we investigate if the responsibility of cellular proliferation is shared equally among the differentiated cells, or are the cells segregated into proliferative and functional (quiescent) sub-populations. We utilize endocrine organs as model systems due to their importance in the metabolic functions of the body. Disorders of thyroid gland and beta-cells (diabetes) inflict almost 100 million and 425 million people worldwide, respectively.
Understanding how cellular communities handle multitasking has implications on translational biology. In an egalitarian model, cells have similar capacities, and thus cellular replacement by regenerative or transplantation therapy would be highly feasible due to the high level of cellular homogeneity. In contrast, a segregated model would require the presence of all cellular sub-populations. The failure of a single sub-population could lead to a systemic breakdown. Identifying the mode of task allocation is important for understanding how organs function and for successfully generating them outside the body.