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Title: Stem cells and their niche in Hensen's node during chick axial development
Author: Solovieva, Tatiana Mikhailovna
ISNI:       0000 0004 9353 4174
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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Axial development in amniotes occurs from a caudal growth zone. Previous work in chick suggested that Hensen’s node contains resident, self-renewing stem cells that generate axial and paraxial tissues along the entire axis. However, it is not clear whether the node represents a stem cell niche that can induce and maintain stem cell behaviour (‘instructive’ stem cell niche). Through a series of heterotopic grafts we show that the node can specify resident cell behaviour in epiblast cells that do not normally enter the node. Single cell transplantation reveals that these can self-renew and contribute to the axis, suggesting that the node can induce and maintain stem cells and therefore acts as an instructive stem cell niche. However, the node is not able to induce any epiblast in this way. When made to enter the node, epiblast from an older donor, while able to contribute to axial and paraxial structures and to cells with resident behaviour, does not always express genes appropriate to its new location, as revealed by in situ hybridisation. Single-cell RNA-seq of identified, individually hand-picked resident cells from control and experimental epiblast grafts (epiblast not normally fated to enter the node) was used to find genes whose expression correlates with cells that are either more or less competent to respond to the node. The RNA-seq also reveals that irrespective of epiblast origin, a cell’s molecular signature appears to reflect its anterior-posterior position within the regressing node. More posterior cells express genes associated with late cell-cycle markers, suggesting they are in the process of dividing. Furthermore, fate maps of regressing node reveal that only posterior cells continue to contribute to cells with resident behaviour as axial development continues, thus raising the possibility that ‘longer-term’ dividing resident stem cells reside in the posterior part of the regressing node.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available