A quantitative analysis of Neuro-mesodermal progenitor cell fate decisions

Garai, Sumit (2023) A quantitative analysis of Neuro-mesodermal progenitor cell fate decisions. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Sumit Garai (18MS062)) Thesis_18MS062.pdf - Submitted Version Restricted to Repository staff only Download (10MB)

Abstract

Despite cell fate decisions being fundamental for developmental processes, many descriptions have remained phenomenological, and hence for many fate decisions a quantitative understanding of differentiation dynamics is lacking. Neuro Mesodermal progenitors (NMPs) are a unique bipotent progenitor cell population found in the early vertebrate embryo - which arises from a pluripotent epiblast-like state and go on to give rise to posterior neural and mesodermal cells. Recent studies have established NMPs to be distinct and stable cellular states with unique molecular and functional characteristics, and suggest that NMP maintenance and decision making relies on the balance of two transcription factors, T and Sox2, under the control of the morphogen WNT. However, a quantitative understanding of how T and Sox2 levels affect differentiation dynamics is lacking. Here, we combined embryonic stem cell lines carrying T and Sox2 reporters, 2D differentiation protocols, and high-resolution live imaging to monitor the NMP decision making process in real-time. We used deep learning to extract morphological parameters and reporter intensity values, enabling the correlation of the cell morphome to the NMP decision making process. Moreover, we conduct a phase portrait analysis of cells from cells undergoing differentiation along the epiblast-NMP-mesoderm trajectory, in order to obtain quantitative insights into the dynamics of the NMP decision making process.

Actions (login required)

View Item