BIOMECHANICS, BIOENGINEERING AND MATHEMATICAL BIOLOGY Seminar

PROGRAM

Plan rada Seminara iz Biomehanike, bioinžinjeringa i matematičke biologije za AVGUST 2023.

SREDA, 16.08.2023. u 16:00, Naučni klub Niš, Pariske komune bb, Niš i Online
Ivana Vasić, Vitra Labs
INVESTIGATING THE RELATIONSHIP BETWEEN CELL STRUCTURE AND SIGNALING IN HUMAN INDUCED PLURIPOTENT STEM CELLS
Early in embryonic development, gradients of signaling molecules guide the spatial organization and specification of stem cells. One of the earliest biological patterning events occurs in the epiblast, when pluripotent cells differentiate and segregate into the three somatic germ layers (endoderm, mesoderm, and ectoderm) in a process known as gastrulation. Just prior to gastrulation, the epiblast is an epithelial tissue reinforced by tight junction complexes. These complexes partition the cell’s phospholipid bilayer into apical and basolateral domains and prevent the diffusion of signaling molecules between the apical-facing and basolateral-facing lumens. Polarized secretion and trafficking of ligands and receptors responsible for signaling during gastrulation implicates epithelial structure and cell polarity as critical determinants of morphogen gradient shape and subsequent cell type patterning. In addition to possible spatial patterning imposed by epithelial structure, previous studies have proposed that signaling molecules can autonomously form patterns, as described by Alan Turing’s reaction diffusion (RD) and Lewis Wolpert’s positional information (PI) mathematical models. However, a lack of mechanistic insight hinders our understanding of the possible interplay between tight junction expression and RD/PI. In this study, we use an in vitro model of gastrulation to study the role of tight junctions and apical/basolateral polarity in modulating bone morphogenic protein-4 (BMP4) signaling and gastrulation-associated patterning in colonies of human pluripotent stem cells. Disrupting tight junctions via knockdown of the scaffolding tight junction protein-1 (TJP1) allows BMP4 to activate pSMAD1/5 signaling robustly and ubiquitously over time, resulting in loss of the patterning phenotype and marked differentiation bias of pluripotent stem cells to primordial germ cell-like cells (PGCLCs). These findings give important insights into how signaling events are regulated and lead to spatial emergence of diverse cell types in vitro.