Independent inheritance of genes regulating two subpopulations of mouse clonogenic keratinocyte stem cells

Natalia V. Popova, Naira E. Suleimanian, Ekaterina A. Stepanova, Kimberly A. Teti, Kai Q. Wu, Rebecca J. Morris

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Mouse keratinocyte stem cells originate from the bulge of hair follicle, and, according to definition, possess a clonogenic activity in vitro. We have investigated seven inbred (C57BL/6, C3H, DBA/2, BALB/c, FVB) and outbred (SENCAR, CD-1) mouse strains and found that three genetically distinct subsets of mouse strains differ significantly in the frequency of clonogenic activity in vitro. The analysis of keratinocyte colonies in two reciprocal backcross [C57BL/6 x (BALB/c x C57BL/6); BALB/c x (BALB/c x C57BL/6)] and intercross [(BALB/c x C57BL/ 6)F2] of BALB/c and C57BL/6 mice allowed us to identify two subpopulations of clonogenic keratinocytes able to produce small (less than 2 mm2) and large (more than 2 mm2) colonies. We conducted linkage analysis and found that small colonies associated with mouse chromosomes 1, 6, 7, 8, and 9; but large colonies - with the chromosome 4. We defined locus on the chromosome 9 that associated with small colonies as keratinocyte stem cell locus 1 (Ksc1), and locus on the mouse chromosome 4 associated with large colonies-keratinocyte stem cell locus 2 (Ksc2). Ksc1 and loci on chromosomes 6 and 7 are close if not equal to loci associated with sensitivity to skin carcinogenesis. We conclude that two subpopulations of stem cells able to produce small and large colonies regulated by different genes and genes regulating small colonies might be responsible for sensitivity to skin carcinogenesis.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalJournal of Investigative Dermatology Symposium Proceedings
Volume9
Issue number3
DOIs
StatePublished - Sep 2004

Bibliographical note

Funding Information:
This work was supported in part by NIH grant CA45293 (RJM) and by the Lankenau Foundation. We thank Dr Spencer M. Free for statistical analysis.

Keywords

  • Clonogenic keratinocytes
  • Genetic mapping
  • Skin carcinogenesis
  • Stem cells

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