How does hair actually form, and what does cell 'death' have to do with it?

BACKGROUND

The transition of hair shaft keratinocytes from living, nucleated cells to structural cells without a nucleus or cytoplasm is essential for hair production. This process, known as cornification, requires the removal of cellular organelles to allow the cytoplasm to pack with keratin filament bundles, which then cross-link to form a strong hair fiber. While well-understood in epidermal keratinocytes, the mechanisms in hair follicles are not as clear.

OBJECTIVE

To gain insights into the mechanisms of cornification within the hair follicle to improve our understanding of normal hair physiology.

METHOD

The study obtained scalp biopsies and hair-pluck samples from healthy human donors. These samples were then analyzed microscopically after immunohistochemical staining. Confocal microscopy was used to capture fluorescent images, and transmission electron microscopy was used for ultrastructural analysis. Various markers were used to assess proliferation, mitochondrial presence, DNA fragmentation, apoptosis, and autophagy.

RESULTS

Evidence of respiratory activity and nuclear damage in keratogenous zone cells was found within the hair shaft. Nuclear degradation occurred through both caspase-dependent and caspase-independent pathways. Mitophagy, the removal of mitochondria, was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe.

CONCLUSION

There is a stepwise living-dead transition in hair formation. Functional, nucleated cells degrade nuclear DNA but continue to respire and provide reactive oxygen species for keratin cross-linking. Eventually, Bnip3L expression triggers mitophagy, removing the last living characteristics, completing the transition from living to dead.

Click here to read the full study >

CONFLICT OF INTEREST STATEMENT

This work was co-funded by Procter and Gamble and Agency for Science, Technology and Research, Singapore