PMID- 24531760
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20220316
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 507
IP  - 7492
DP  - 2014 Mar 20
TI  - Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live 
      imaging.
PG  - 362-365
LID - 10.1038/nature12972 [doi]
AB  - The rapid turnover of the mammalian intestinal epithelium is supported by stem 
      cells located around the base of the crypt. In addition to the Lgr5 marker, 
      intestinal stem cells have been associated with other markers that are expressed 
      heterogeneously within the crypt base region. Previous quantitative clonal fate 
      analyses have led to the proposal that homeostasis occurs as the consequence of 
      neutral competition between dividing stem cells. However, the short-term 
      behaviour of individual Lgr5(+) cells positioned at different locations within 
      the crypt base compartment has not been resolved. Here we establish the 
      short-term dynamics of intestinal stem cells using the novel approach of 
      continuous intravital imaging of Lgr5- Confetti mice. We find that Lgr5(+) cells 
      in the upper part of the niche (termed 'border cells') can be passively displaced 
      into the transit-amplifying domain, after the division of proximate cells, 
      implying that the determination of stem-cell fate can be uncoupled from division. 
      Through quantitative analysis of individual clonal lineages, we show that stem 
      cells at the crypt base, termed 'central cells', experience a survival advantage 
      over border stem cells. However, through the transfer of stem cells between the 
      border and central regions, all Lgr5(+) cells are endowed with long-term 
      self-renewal potential. These findings establish a novel paradigm for stem-cell 
      maintenance in which a dynamically heterogeneous cell population is able to 
      function long term as a single stem-cell pool.
FAU - Ritsma, Laila
AU  - Ritsma L
AD  - Hubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 
      CT, Utrecht, the Netherlands.
AD  - Cancer Genomics Netherlands.
FAU - Ellenbroek, Saskia I J
AU  - Ellenbroek SIJ
AD  - Hubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 
      CT, Utrecht, the Netherlands.
AD  - Cancer Genomics Netherlands.
FAU - Zomer, Anoek
AU  - Zomer A
AD  - Hubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 
      CT, Utrecht, the Netherlands.
AD  - Cancer Genomics Netherlands.
FAU - Snippert, Hugo J
AU  - Snippert HJ
AD  - Cancer Genomics Netherlands.
AD  - University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, the 
      Netherlands.
FAU - de Sauvage, Frederic J
AU  - de Sauvage FJ
AD  - Department of Molecular Biology, Genentech Inc, 1 DNA Way, South San Francisco, 
      CA 94080, USA.
FAU - Simons, Benjamin D
AU  - Simons BD
AD  - Cavendish Laboratory, Department of Physics, J.J. Thomson Avenue, University of 
      Cambridge, Cambridge CB3 0HE, UK.
AD  - The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, 
      Tennis Court Road, Cambridge CB2 1QN, UK.
AD  - Wellcome Trust-Medical Research Council Stem Cell Institute, University of 
      Cambridge, UK.
FAU - Clevers, Hans
AU  - Clevers H
AD  - Hubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 
      CT, Utrecht, the Netherlands.
AD  - Cancer Genomics Netherlands.
FAU - van Rheenen, Jacco
AU  - van Rheenen J
AD  - Hubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 
      CT, Utrecht, the Netherlands.
AD  - Cancer Genomics Netherlands.
LA  - eng
GR  - 092096/Wellcome Trust/United Kingdom
GR  - 098357/Wellcome Trust/United Kingdom
GR  - 13-0297/AICR_/Worldwide Cancer Research/United Kingdom
GR  - Wellcome Trust/United Kingdom
GR  - 098357/Z/12/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140216
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
SB  - IM
CIN - Cell Stem Cell. 2014 Mar 6;14(3):271-3. doi: 10.1016/j.stem.2014.02.011. PMID: 
      24607401
MH  - Animals
MH  - Cell Division
MH  - Cell Lineage
MH  - Cell Survival
MH  - Clone Cells/cytology
MH  - Female
MH  - *Homeostasis
MH  - Intestinal Mucosa/*cytology
MH  - Male
MH  - Mice
MH  - Models, Biological
MH  - Molecular Imaging
MH  - Receptors, G-Protein-Coupled/genetics/metabolism
MH  - *Single-Cell Analysis
MH  - Stem Cells/*cytology
PMC - PMC3964820
MID - EMS56127
OID - NLM: EMS56127
EDAT- 2014/02/18 06:00
MHDA- 2014/04/09 06:00
PMCR- 2014/09/20
CRDT- 2014/02/18 06:00
PHST- 2013/05/30 00:00 [received]
PHST- 2013/12/20 00:00 [accepted]
PHST- 2014/02/18 06:00 [entrez]
PHST- 2014/02/18 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
PHST- 2014/09/20 00:00 [pmc-release]
AID - 10.1038/nature12972 [doi]
PST - ppublish
SO  - Nature. 2014 Mar 20;507(7492):362-365. doi: 10.1038/nature12972. Epub 2014 Feb 
      16.