PMID- 18650388
OWN - NLM
STAT- MEDLINE
DCOM- 20080828
LR  - 20220316
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 30
DP  - 2008 Jul 29
TI  - Generation of mTert-GFP mice as a model to identify and study tissue progenitor 
      cells.
PG  - 10420-5
LID - 10.1073/pnas.0804800105 [doi]
AB  - Stem cells hold great promise for regenerative medicine, but remain elusive in 
      many tissues in part because universal markers of "stemness" have not been 
      identified. The ribonucleoprotein complex telomerase catalyzes the extension of 
      chromosome ends, and its expression is associated with failure of cells to 
      undergo cellular senescence. Because such resistance to senescence is a common 
      characteristic of many stem cells, we hypothesized that telomerase expression may 
      provide a selective biomarker for stem cells in multiple tissues. In fact, 
      telomerase expression has been demonstrated within hematopoietic stem cells. We 
      therefore generated mouse telomerase reverse transcriptase (mTert)-GFP-transgenic 
      mice and assayed the ability of mTert-driven GFP to mark tissue stem cells in 
      testis, bone marrow (BM), and intestine. mTert-GFP mice were generated by using a 
      two-step embryonic stem cell-based strategy, which enabled primary and secondary 
      screening of stably transfected clones before blastocyst injection, greatly 
      increasing the probability of obtaining mTert reporter mice with physiologically 
      appropriate regulation of GFP expression. Analysis of adult mice showed that GFP 
      is expressed in differentiating male germ cells, is enriched among BM-derived 
      hematopoietic stem cells, and specifically marks long-term BrdU-retaining 
      intestinal crypt cells. In addition, telomerase-expressing GFP(+) BM cells showed 
      long-term, serial, multilineage BM reconstitution, fulfilling the functional 
      definition of hematopoietic stem cells. Together, these data provide direct 
      evidence that mTert-GFP expression marks progenitor cells in blood and small 
      intestine, validating these mice as a useful tool for the prospective 
      identification, isolation, and functional characterization of progenitor/stem 
      cells from multiple tissues.
FAU - Breault, David T
AU  - Breault DT
AD  - Divisions of Endocrinology and Gastroenterology, Children's Hospital Boston, 
      Harvard Medical School, Boston, MA 02115, USA. 
      david.breault@childrens.harvard.edu
FAU - Min, Irene M
AU  - Min IM
FAU - Carlone, Diana L
AU  - Carlone DL
FAU - Farilla, Loredana G
AU  - Farilla LG
FAU - Ambruzs, Dana M
AU  - Ambruzs DM
FAU - Henderson, Daniel E
AU  - Henderson DE
FAU - Algra, Selma
AU  - Algra S
FAU - Montgomery, Robert K
AU  - Montgomery RK
FAU - Wagers, Amy J
AU  - Wagers AJ
FAU - Hole, Nicholas
AU  - Hole N
LA  - eng
GR  - 5T32 DK007699/DK/NIDDK NIH HHS/United States
GR  - R01 DK084056/DK/NIDDK NIH HHS/United States
GR  - T32 DK007260/DK/NIDDK NIH HHS/United States
GR  - R37 DK032658/DK/NIDDK NIH HHS/United States
GR  - P30 HD018655/HD/NICHD NIH HHS/United States
GR  - K08 DK066305/DK/NIDDK NIH HHS/United States
GR  - P30 HD18655/HD/NICHD NIH HHS/United States
GR  - R37 DK32658/DK/NIDDK NIH HHS/United States
GR  - T32 DK007699/DK/NIDDK NIH HHS/United States
GR  - 2T32 DK07260/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080723
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Biomarkers)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.7.49 (Telomerase)
RN  - EC 2.7.7.49 (Tert protein, mouse)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Bone Marrow/metabolism
MH  - Cell Separation
MH  - Embryonic Stem Cells/*cytology
MH  - *Genetic Techniques
MH  - Green Fluorescent Proteins/*metabolism
MH  - Intestinal Mucosa/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Phenotype
MH  - Stem Cells/*cytology
MH  - Telomerase/*metabolism
MH  - Testis/metabolism
PMC - PMC2492454
COIS- The authors declare no conflict of interest.
EDAT- 2008/07/25 09:00
MHDA- 2008/08/30 09:00
PMCR- 2009/01/29
CRDT- 2008/07/25 09:00
PHST- 2008/07/25 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/07/25 09:00 [entrez]
PHST- 2009/01/29 00:00 [pmc-release]
AID - 0804800105 [pii]
AID - 4099 [pii]
AID - 10.1073/pnas.0804800105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10420-5. doi: 
      10.1073/pnas.0804800105. Epub 2008 Jul 23.