Gene Expression Profiling Of The Intact Dermal Sheath Cup Of Human Hair Follicles

[cocona]

http://www.medicaljournals.se/acta/content/html/10.2340/00015555-2949

New paper from Shiseido:

Gene expression map based on different parts of the hair follicle.

Abbreviations key:
DP- Dermal Papilla
DSC- Dermal Sheath Cup
UDS- Upper Dermal Sheath

Discussion:
This study compared the gene expression profiles of 3 different mesenchymal subunits of the human HF, the DSC, DP and UDS, which were isolated by microdissection. A DSC signature containing 32 genes was identified, which may be regulated by TGF-b1, Wnt and BMP signalling molecules. Among the DSC signature genes, alpha-SMA, matrix metallopeptidase 11 and prostaglandin E receptor 3 have been reported to be expressed in the DS (24, 26, 27, 28).

Furthermore, this study identified 113 DP signature genes from 127 probes that were up-regulated in the DP compared with the DSC (Table I, Table SII). DP signatures reported previously by 3 groups, and a dermal condensation signature (17–20), respectively, included 18, 12, 19 and 10 genes in common with our results (Table IV). These similarities suggest that the novel signature genes identified are specific to, and characteristic of, each mesenchymal subunit of the HF.

It is noteworthy that TGF-b1 was identified as a putative upstream regulator of the DSC signature genes. TGF-b1 is a well-known regulator of extracellular matrix expression, has previously been reported to be expressed in the DS of human HF, and can regulate the reactivation of DP cells by androgens (29–31). On the other hand, the results of the current study suggest that characteristic extracellular matrix components are expressed in the DSC. In addition, DS cells have been reported to show a distinct profile of matrix metalloproteinases (32, 33). Thus, TGF-b1 may play a role in regulating DSC matrix characteristics. Al-though the origin of the DSC remains unclear, considering that GREM1 and GREM2 are expressed in both mouse embryonic skin and human HF, it is possible that they could play a role in the early stage of DSC formation. In the present study, 3 genes, GREM2, retinoic acid binding protein 4, together with the Wnt signalling molecule TLE4, showed relative higher expression levels in the DSC compared with the DP or DS (Fig. 4, Table SIII). Interestingly, a recent study reported that mesenchymal-derived GREM1 plays a crucial role in feather formation accompanying signalling modulation by Wnt-3a and retinoic acid (34), thus these 3 molecules, including GREM, may be involved in the functioning of the DSC during the hair cycle and hair morphogenesis.

This report identified several signature genes of the DSC and showed specific localization within DSC of one of them, revealing the molecular mechanisms that contribute to acquisition of the characteristic features of the human DSC, which could be useful for understanding the biology of the human HF.

Notes:
- Prostaglandin E receptor 3 is activated by Castor Oil(Retinoic acid)
- Targets of opportunity in the DSC (GREM, Wnt signalling molecule TLE4, retinoic acid binding protein 4)
a. DSC activation is important as it is the area where progenitor cells are contained although there may also be some progenitor cells in the dermal sheath as well.
- Previous gene maps have shown TGF-B is upregulated In the Androgenetic Alopecia scalp this can mean TGF-B is being over transcripted or under activated.