“Different Skin Tumors Come From Different Stem Cells Located in The Epidermis”
Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity.
Kretzschmar K, Weber C, Driskell RR, Calonje E, Watt FM.
Cell Rep. 2016 Jan 12;14(2):269-81. doi: 10.1016/j.celrep.2015.12.041. Epub 2016 Jan 7
-This study from the UK sought to determine stem cell location as well as define roles of subtypes of stem cells in normal and pathological conditions.
What do we learn from this article ?
1. The Wnt/ Beta-Catenin pathway plays a crucial role in epidermal development, homeostasis, and cancer.
2. Different differentiated stem cells occupy a specific location of the epidermis:
-LGR6+ are located in the upper hair follicle and epidermis
-LRIG1+ are located in the upper hair follicle
-LGR5+ are located in the lower hair follicle
3. Subtle changes on B-Catenin signalling on Stem Cells with different markers lead to different phenotypes:
A. In a “constructive way” = hair follicle formation
-LGR6(+) and LRIG1(+) stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation.
-Lgr6, (but not Lrig1 or Lgr5), was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles.
B. Skin tumors (benign) can arise when the Wnt/ Beta-Catenin pathway is oncogenic:
-LGR5(+) cells led to formation of pilomatricomas.
-LRIG1(+) cells formed trichoadenomas.
-LGR6(+) cells formed dermatofibromas.
-This study was done in mice
–Dermatofibromas may actually originate from the epidermis from Stem Cells located on the upper part of hair follicles.
Clincal Correlations and questions
-Pilomatricoma accurs more frequently in children. Are LGR5+ stem cells more present or active in this population group ?
-Dermatofibromas are more frequent in women and on the lower legs. Are LGR6(+) cells more frequent accordingly in both humans and mice ?
The “Stem cell” word
-More generally it tells us that the term “Stem Cell” is vague and even if it is clear to us, the public is generally unaware that they can range from embryonic totipotent stem cells to tissue specific stem cells !
-Also worthy of note; pluripotent stem cells in adults may not exist and using the term adult stem cell only adds confusion and this study shows again that after bhirth, all will have been programmed to follow some specific developmental pathway during embryogenesis.
Article selected by Saurat JH, MD