Solovieva, Tatiana Mikhailovna;
(2020)
Stem cells and their niche in Hensen's node during chick axial development.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Stem cells and their niche in Hensen's node during chick axial development |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10106272 |
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