Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells.
Regulation of stem cell (SC) proliferation is central to tissue homoeostasis, injury repair, and cancer development. Accumulation of replication errors in SCs is limited by either infrequent division and/or by chromosome sorting to retain preferentially the oldest 'immortal' DNA strand. The frequency of SC divisions and the chromosome-sorting phenomenon are difficult to examine accurately with existing methods. To address this question, we developed a strategy to count divisions of hair follicle (HF) SCs over time, and provide the first quantitative proliferation history of a tissue SC during its normal homoeostasis. We uncovered an unexpectedly high cellular turnover in the SC compartment in one round of activation. Our study provides quantitative data in support of the long-standing infrequent SC division model, and shows that HF SCs do not retain the older DNA strands or sort their chromosome. This new ability to count divisions in vivo has relevance for obtaining basic knowledge of tissue kinetics.
Waghmare
Sanjeev K
SK
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
Bansal
Rajat
R
Lee
Jayhun
J
Zhang
Ying V
YV
McDermitt
David J
DJ
Tumbar
Tudorita
T
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation; D020090:Chromosome Segregation; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D006657:Histones; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C431843:tris(2-pyridylmethyl)amine; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine