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theses

Neurogenesis is a complex process which is controlled by intrinsic programs and exogenous signals among the cells resulting in formation of progressively committed neurons. The complex processes governing neurogenesis can be elucidated by determining the developmental stages and compositions of the cells along with their molecular determinants. The single cell RNA sequencing (scRNA-seq) study of undifferentiated neural precursor cells ultimately differentiating into neurons is an effort to understand these mechanisms. This study is performed on a dataset (GEO accession #GSE102066) consisting of four cell types, i.e., neural precursor cell, differentiating neural cell, immature neuron and neuron. A comprehensive analysis examining the trajectory path of neural precursor cells to neurons, the highest expressed genes and marker genes of each cell type and the gene ontology (GO) terms associated with these genes has revealed critical observations. Lack of similar intrinsic properties revealed heterogeneity among immature neurons and neurons through trajectory analysis. The genes which were expressed highest among all the cell types was associated with GO term for housekeeping genes which are crucial for maintaining cell functions. The marker genes of each cell type were associated with many relevant GO terms such as neurogenesis, neuron projection, olfactory lobe development, forebrain generation of neurons and central nervous system development. Key factors having discrete gene expression activity as cells transitioned from one state to another were revealed in this study. Genes which drastically decreased their expression levels over a period of two days (day 5 to day 7) were SFRP1 and SFRP2, genes which gradually decreased their expression activity from day 0 to day 30 were WNT5A and EFNA5, known neuronal marker genes DCX, MAP2 and STMN2 were upregulated gradually as the cells reached mature neuron stage. This study has helped in revealing transcriptional profiles of cells differentiating through a critical period of time with the key genes responsible for maintaining cell states and determining cell fates.

ETD_9141

M.S.

Includes bibliographical references

by Satya Pavitra Rani

doi:10.7282/t3-6az6-ba55

ETD graduate

The author owns the copyright to this work.