Epigenetic mechanisms play an important role during the morphogenesis
of the hair follicle and the hair cycle. Work on hair regeneration is of
importance as no products are available which can provide complete
reversal of hair loss. Tet2 promotes DNA demethylation by the
hydroxylation of 5mC to 5hmC which in turn causes gene transcription
activation. Dermal papilla (DP) cells located within the hair follicle are
responsible for the regulation of development and the growth of hair
follicles. Fgf20 signalling controls commitment of the mesenchymal
precursor cells to the DP progenitor lineage. An immature DP cells is then
formed during maturation by Shh signalling which then stimulates these to
differentiate into a DP cell by BMP and Wnt signalling.
Methylated DNA can be bound by the proteins recruiting transcription corepressors.
DNA methyltransferases (DNMT’s) can be degraded by
decitabine which reverses gene silencing. Conditional knockout of Tet2 in
mouse DP cells results in a delay in anagen initiation, suggesting Tet2 is
involved in the telogen-anagen transition. Additionally, by using dermal
fibroblasts and RA-DPAC (Dermal Papilla activating medium
supplemented with retinoic acid), it was found that decitabine can increase
plasticity in dermal fibroblasts and RA-DPAC can be used to accelerate a
lineage change to DP cells which is supported by the significant increase in the DP specific gene expression. Examples include AlPl, LEF1,
BMP4/6/7, FGF10, BMPR1A and PDGFA. Additionally, by way of siRNA
and conditional Tet2 knockout data in dermal fibroblasts, it was found Tet2
regulates signature DP genes such as Bmpr1a, ALPL, Tcf4 and SOX2.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/19881 |
| Date | January 2022 |
| Creators | Ahmed, Aqib |
| Contributors | Mardaryev, Andrei N., Thornton, M. Julie, Botchkarev, Vladimir A., Fessing, Michael Y., Botchkareva, Natalia V. |
| Publisher | University of Bradford, Centre for Skin Sciences. Faculty of Life Science |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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