title: SACK-expanded hair follicle stem cells display asymmetric nuclear Lgr5 expression with non-random sister chromatid segregation.
abstract: We investigated the properties of clonally-expanded mouse hair follicle stem cells (HF-SCs) in culture. The expansion method, suppression of asymmetric cell kinetics (SACK), is non-toxic and reversible, allowing evaluation of the cells' asymmetric production of differentiating progeny cells. A tight association was discovered between non-random sister chromatid segregation, a unique property of distributed stem cells (DSCs), like HF-SCs, and a recently described biomarker, Lgr5. We found that nuclear Lgr5 expression was limited to the HF-SC sister of asymmetric self-renewal divisions that retained non-randomly co-segregated chromosomes, which contain the oldest cellular DNA strands, called immortal DNA strands. This pattern-specific Lgr5 association poses a potential highly specific new biomarker for delineation of DSCs. The expanded HF-SCs also maintained the ability to make differentiated hair follicle cells spontaneously, as well as under conditions that induced cell differentiation. In future human cell studies, this capability would improve skin grafts and hair replacement therapies.
authors.affiliation: Programs in Regenerative Biology and Cancer Biology, Adult Stem Cell Technology Center, Boston Biomedical Research Institute,64 Grove Street, Watertown, MA, USA.
authors.forename: Yang Hoon
authors.initials: YH
authors.lastname: Huh
authors.forename: Johnathan
authors.initials: J
authors.lastname: King
authors.forename: Justin
authors.initials: J
authors.lastname: Cohen
authors.forename: James L
authors.initials: JL
authors.lastname: Sherley
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation; D015638:Cytochalasin D / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D000078404:Epidermal Cells; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000166:cytology*; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D015638:Cytochalasin D; D004247:DNA