A systems biology study to understand the dynamics of progenitor cells populations in the tissue development

Abstract

Embryonic development begins with a cell formed by the union of two sex cells, and ends with a multicellular organism with specialized and diverse functions and shapes. Organogenesis is the integration of spatial and temporal programs with the purpose to generate the mature version of the organ. Concretely, some tissues as the Neural Retina, the Pigmentary Epithelium of the Retina, the Spinal Cord or the Neocortex comes from the anterior region of the neural tube, a structure whose origin is the anterior axis of the embryonic layer of the ectoderm (neuroectoderm). For an important part of all these tissues, the molecular processes that underlie cellular decisions have been extensively characterized. Basically, three activities must happen in the tissue development: the growing in size (proliferation), the specialization in one or more specific functions (differentiate) and the coordination of cell movements to acquire a specific final shape (morphogenesis). Progenitor cells are those cells that have the ability to divide and increase the number of cells, while differentiated cells are those that have acquired a specific function and they are not able to divide into new cells. The action of the whole set of progenitor cells is the responsible to regulate the number of new differentiated and progenitor cells (proliferation), while the sets of differentiated cells is the responsible of the acquisition of specific function. In fact, the function of the organ and the ability to increase in growth or produce more cells (i.e balance between growth and differentiation) can not only be interpreted as the sum of function of each cell. Therefore, research about the behaviour, regulation and properties for all populations of progenitor cells is key to understanding the balance between proliferation (the system generates new progenitor cells) and differentiation (the system generates new differentiated cells) of the embryo development. The descents of the progenitor cells pool along the development regulates the rate between proliferation and differentiation of the tissue. Therefore, it is not only essential to understand the biology of progenitor and differentiated cells, but it is also essential to understand how the union of many progenitor cells works to form a complex system, such as a tissue or an organ. In this thesis, I will intend to answer two major questions: how the proliferation and differentiation of progenitor cell pools is regulated in space-time? And how can we use quantitative tools to analyze this balance?. To do this, we have used two model organisms (Danio rerio and Mus musculus), a theoretical approach based on Markov’s chains, and we have developed computational analysis tools for biological images