Sharif Digital Repository

The molecular mechanisms of self-organization that orchestrate embryonic cells to create astonishing patterns have been among major questions of developmental biology. It is recently shown that embryonic stem cells (ESCs), when cultured in particular micropatterns, can self-organize and mimic the early steps of pre-implantation embryogenesis. A systems-biology model to address this observation from a dynamical systems perspective is essential and can enhance understanding of the phenomenon. Results: Here, we propose a multicellular mathematical model for pattern formation during in vitro gastrulation of human ESCs. This model enhances the basic principles of Waddington epigenetic landscape... 

Background: Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on... 

Retinal pigment epithelial (RPE) cells are indispensable for eye organogenesis and vision. To realize the therapeutic potential of in vitro-generated RPE cells for cell-replacement therapy of RPE-related retinopathies, molecular mechanisms of RPE specification and maturation need to be investigated. So far, many attempts have been made to decipher the regulatory networks involved in the differentiation of human pluripotent stem cells into RPE cells. Here, we exploited a highly-efficient RPE differentiation protocol to determine global expression patterns of microRNAs (miRNAs) during human embryonic stem cell (hESC) differentiation into RPE using small RNA sequencing. Our results revealed a... 

Oxidative stress has been implicated in the progression of age-related macular degeneration (AMD). Treatment with antioxidants seems to delay progression of AMD. In this study, we suggested an antioxidant delivery system based on redox-sensitive liposome composed of phospholipids and a diselenide centered alkyl chain. Dynamic light scattering assessment indicated that the liposomes had an average size of 140 nm with a polydispersity index below 0.2. The percentage of encapsulation efficiency of the liposomes was calculated by high-performance liquid chromatography. The carriers were loaded with N-acetyl cysteine as a model antioxidant drug. We demonstrated responsiveness of the nanocarrier... 

Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the “miRNome” of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most “ground-state miRNAs” are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the...