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Neuronal differentiation and subtype specification in embryonic stem cells

Shodhganga@INFLIBNET

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Title Neuronal differentiation and subtype specification in embryonic stem cells

 
Contributor Mani, Shyamala
 
Subject Electrophoretic mobility shift assays (EMSAs)
Embryoid bodies (EBs)
embryonic stem (ES) cells
Neurogenins (Ngn)
serotonergic neurons
serotonin transporter (SERT)
 
Description Neurogenesis occurs in all mammals throughout life in discrete region of
newlinethe central nervous system (CNS). The process of neurogenesis starts
newlinefrom cells called stem cells which can give rise to multiple lineages and cell
newlinetypes that constitute a mature organ. Through the process of differentiation
newlinestem cells give rise to neurons and glia. The pathway leading to
newlinedifferentiation of stem cells to neurons and glial cells is still not well
newlineunderstood.
newlineIn the present study I have tried to delineate the molecular
newlinemechanism behind the process of differentiation of embryonic stem (ES)
newlinecells to form functional neurons. I have used ES cells as a model for this
newlinestudy. From previous studies it has been known that the interaction of two
newlinefactors the intrinsic determinants and the extrinsic signaling molecules play
newlinean important role in the process of neuronal differentiation. To analyze the
newlinerole of intrinsic determinants in this study I have demonstrated that during
newlinethe process of neuronal differentiation, the expression of neurogenin2
newline(Ngn2) increases as human ES cells are differentiated towards the
newlineneuroepithelial lineage. When embryoid bodies (EBs) are treated with the
newlineneural inducers vasoactive intestinal peptide (VIP) or retinoic acid (RA), the
newlineexpression of Ngn2 increased in EBs and in neurospheres (NS). However,
newlinethe expression of Ngn2 was not homogenous in EBs. The TH (tyrosine
newlinehydroxylase) positive neurons that were derived from VIP or RA exposed
newlineEBs correlated with the proportion of Ngn2 positive cells that were present
newlinein EBs and NS. This suggests that Ngn2 plays a role in determining
newlinedopaminergic neuron phenotype during the process of neuronal
newlinedifferentiation.
newline
newlineThe role of extrinsic factors was studied during differentiation of hES
newlinecells into serotonin neurons. Differentiation of stem cells into serotonin
newlineneurons has not been well characterized. Homogeneous neural progenitors
newlinewere isolated from differentiating hES cells. These homogeneous neural
newlineprogenitors were differentiated into serotonin containing neuro

 
Date 2018-09-27T05:31:47Z
2018-09-27T05:31:47Z
2002
2008

 
Type Ph.D.
 
Identifier http://hdl.handle.net/10603/217685
 
Language English
 
Relation
 
Rights university
 
Format

DVD
 
Coverage
 
Publisher Gurugram
National Brain Research Centre
Department of Neuroscience
 
Source University