Apoptotic cells may drive cell death in hair follicles during their regression cycle
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Bradley D. Keister1, Kailin R. Mesa2,3 and Krastan B. Blagoev1,4,5,6
1 National Science Foundation, Physics Division, Alexandria, VA 22230, USA
2 The Jane Coffin Childs Memorial Fund for Medical Research, New Haven, CT 06520, USA
3 Department of Genetics and Dermatology, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06510, USA
4 Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA
5 Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria
6 Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR3664, Laboratoire Dynamique du Noyau, Paris 75005, France
|Krastan B. Blagoev,||email:||[email protected]|
Keywords: hair follicle; stem cells; regression cycle; mathematical model; analysis
Received: June 13, 2023 Accepted: September 21, 2023 Published: October 19, 2023
Intravital microscopy in live mice has shown that the elimination of epithelial cells during hair follicle regression involves supra-basal cell differentiation and basal cell apoptosis through synergistic action of TGF-β (transforming growth factor) and mesenchymal-epithelial interactions. In this process the basal epithelial cells are not internally committed to death and the mesenchymal dermal papilla (DP) plays essential role in death induction. Because the DP cells are not necessary for completion of the cycle but only for its initiation it is still an open question what is the mechanism leading to the propagation of apoptosis towards the regenerative stem cell population. Here, we use a quantitative analysis of the length of hair follicles during their regression cycle. The data are consistent with a propagation mechanism driven by apoptotic cells inducing apoptosis in their neighboring cells. The observation that the apoptosis slows down as the apoptotic front approaches the stem cells at the end of the follicle is consistent with a gradient of a pro-survival signal sent by these stem cells. An experiment that can falsify this mechanism is proposed.
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