Open AccessFunctional Characterization of Quiescent Keratinocyte Stem Cells and Their Progeny Reveals a Hierarchical Organization in Human Skin Epidermis
Author(s) -
Schlüter Holger,
PaquetFifield Sophie,
Gangatirkar Pradnya,
Li Jason,
Kaur Pritinder
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.675
Subject(s) - biology , epidermis (zoology) , stem cell , keratinocyte , microbiology and biotechnology , progenitor cell , population , cellular differentiation , in vitro , anatomy , genetics , gene , demography , sociology
Although homeostatic renewal of human skin epidermis is achieved by the combined activity of quiescent stem cells (SCs) and their actively cycling progeny, whether these two populations are equipotent in their capacity to regenerate tissue has not been determined in biological assays that mimic lifelong renewal. Using fluorescence activated cell separation strategy validated previously by us, human epidermis was fractionated into three distinct subsets: that is, α 6 bri CD71 dim , α 6 bri CD71 bri , and α 6 dimwith characteristics of keratinocyte stem, transient amplifying, and early differentiating cells, respectively. The global gene expression profile of these fractions was determined by microarray, confirming that the α 6 bri CD71 dim subset was quiescent, the α 6 bri CD71 bri was actively cycling, and the α 6 dimsubset expressed markers of differentiation. More importantly, functional evaluation of these populations in an in vivo model for tissue reconstitution at limiting cell dilutions revealed that the quiescent α 6 bri CD71 dim fraction was the most potent proliferative and tissue regenerative population of the epidermis, capable of long‐term (LT) epidermal renewal from as little as 100 cells for up to 10 weeks. In contrast, the cycling α 6 bri CD71 bri fraction was the first to initiate tissue reconstitution, although this was not sustained in the LT, while differentiating α 6 dimcells possessed the lowest demonstrable tissue regenerative capacity. Our data suggest that in human skin, the epidermal proliferative compartment is not composed of equipotent cells, but rather is organized in a functionally hierarchical manner with the most potent quiescent SCs at its apex (i.e., α 6 bri CD71 dim ) followed by cycling progenitors (i.e., α 6 bri CD71 bri ) and finally early differentiating keratinocytes (i.e., α 6 dim ). S TEM C ELLS 2011;29:1256–1268