title: Defining the cellular lineage hierarchy in the interfollicular epidermis of adult skin.
abstract: The interfollicular epidermis regenerates from heterogeneous basal skin cell populations that divide at different rates. It has previously been presumed that infrequently dividing basal cells known as label-retaining cells (LRCs) are stem cells, whereas non-LRCs are short-lived progenitors. Here we employ the H2B-GFP pulse-chase system in adult mouse skin and find that epidermal LRCs and non-LRCs are molecularly distinct and can be differentiated by Dlx1(CreER) and Slc1a3(CreER) genetic marking, respectively. Long-term lineage tracing and mathematical modelling of H2B-GFP dilution data show that LRCs and non-LRCs constitute two distinct stem cell populations with different patterns of proliferation, differentiation and upward cellular transport. During homeostasis, these populations are enriched in spatially distinct skin territories and can preferentially produce unique differentiated lineages. On wounding or selective killing, they can temporarily replenish each other's territory. These two discrete interfollicular stem cell populations are functionally interchangeable and intrinsically well adapted to thrive in distinct skin environments.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sada
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Jacob
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Leung
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Oncology, Department of Medicine, Washington University, St Louis, Missouri 63110, USA.|McDonnell Genome Institute, Washington University, St Louis, Missouri 63110, USA.
authors.forename: Brian S
authors.identifier: 0000-0002-2954-4410
authors.initials: BS
authors.lastname: White
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shalloway
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Tudorita
authors.initials: T
authors.lastname: Tumbar
mesh_terms: D000375:Aging; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D000078404:Epidermal Cells; D020869:Gene Expression Profiling / Q000379:methods; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D012867:Skin / Q000166:cytology*; D013194:Staining and Labeling / Q000379:methods; D013234:Stem Cells / Q000166:cytology*