PMID- 21927002
OWN - NLM
STAT- MEDLINE
DCOM- 20120125
LR  - 20220318
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 478
IP  - 7368
DP  - 2011 Sep 18
TI  - A reserve stem cell population in small intestine renders Lgr5-positive cells 
      dispensable.
PG  - 255-9
LID - 10.1038/nature10408 [doi]
AB  - The small intestine epithelium renews every 2 to 5 days, making it one of the 
      most regenerative mammalian tissues. Genetic inducible fate mapping studies have 
      identified two principal epithelial stem cell pools in this tissue. One pool 
      consists of columnar Lgr5-expressing cells that cycle rapidly and are present 
      predominantly at the crypt base. The other pool consists of Bmi1-expressing cells 
      that largely reside above the crypt base. However, the relative functions of 
      these two pools and their interrelationship are not understood. Here we 
      specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin 
      receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of 
      the Lgr5-expressing cells did not perturb homeostasis of the epithelium, 
      indicating that other cell types can compensate for the elimination of this 
      population. After ablation of Lgr5-expressing cells, progeny production by 
      Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells 
      compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed 
      that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a 
      hierarchy of stem cells in the intestinal epithelium. Our results demonstrate 
      that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and 
      that in the absence of these cells, Bmi1-expressing cells can serve as an 
      alternative stem cell pool. These data provide the first experimental evidence 
      for the interrelationship between these populations. The Bmi1-expressing stem 
      cells may represent both a reserve stem cell pool in case of injury to the small 
      intestine epithelium and a source for replenishment of the Lgr5-expressing cells 
      under non-pathological conditions.
FAU - Tian, Hua
AU  - Tian H
AD  - Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, 
      California 94080, USA.
FAU - Biehs, Brian
AU  - Biehs B
FAU - Warming, Soren
AU  - Warming S
FAU - Leong, Kevin G
AU  - Leong KG
FAU - Rangell, Linda
AU  - Rangell L
FAU - Klein, Ophir D
AU  - Klein OD
FAU - de Sauvage, Frederic J
AU  - de Sauvage FJ
LA  - eng
GR  - DP2 OD007191/OD/NIH HHS/United States
GR  - R01 DE021420/DE/NIDCR NIH HHS/United States
GR  - R01-DE021420/DE/NIDCR NIH HHS/United States
GR  - 1-DP2-OD007191/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110918
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Bmi1 protein, mouse)
RN  - 0 (HBEGF protein, human)
RN  - 0 (Hbegf protein, mouse)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Repressor Proteins)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
SB  - IM
EIN - Nature. 2012 Feb 2;482(7383):120
CIN - Cell Stem Cell. 2012 Jan 6;10(1):2-4. doi: 10.1016/j.stem.2011.12.012. PMID: 
      22226346
MH  - Animals
MH  - Cell Lineage
MH  - Epithelial Cells/cytology/metabolism
MH  - Female
MH  - Heparin-binding EGF-like Growth Factor
MH  - Homeostasis
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Intestine, Small/*cytology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nuclear Proteins/*metabolism
MH  - Polycomb Repressive Complex 1
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Receptors, G-Protein-Coupled/deficiency/genetics/*metabolism
MH  - Regeneration
MH  - Repressor Proteins/*metabolism
MH  - Stem Cells/*cytology/metabolism
PMC - PMC4251967
MID - NIHMS643813
EDAT- 2011/09/20 06:00
MHDA- 2012/01/26 06:00
PMCR- 2014/12/02
CRDT- 2011/09/20 06:00
PHST- 2011/04/19 00:00 [received]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/01/26 06:00 [medline]
PHST- 2014/12/02 00:00 [pmc-release]
AID - nature10408 [pii]
AID - 10.1038/nature10408 [doi]
PST - epublish
SO  - Nature. 2011 Sep 18;478(7368):255-9. doi: 10.1038/nature10408.