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Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 105, 2008, 30, S. 10420-10425 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Breault, David T. Min, Irene M. Carlone, Diana L. Farilla, Loredana G. Ambruzs, Dana M. Henderson, Daniel E. Algra, Selma Montgomery, Robert K. Wagers, Amy J. Hole, Nicholas Breault, David T. Min, Irene M. Carlone, Diana L. Farilla, Loredana G. Ambruzs, Dana M. Henderson, Daniel E. Algra, Selma Montgomery, Robert K. Wagers, Amy J. Hole, Nicholas |
|---|---|
| author |
Breault, David T. Min, Irene M. Carlone, Diana L. Farilla, Loredana G. Ambruzs, Dana M. Henderson, Daniel E. Algra, Selma Montgomery, Robert K. Wagers, Amy J. Hole, Nicholas |
| spellingShingle |
Breault, David T. Min, Irene M. Carlone, Diana L. Farilla, Loredana G. Ambruzs, Dana M. Henderson, Daniel E. Algra, Selma Montgomery, Robert K. Wagers, Amy J. Hole, Nicholas Proceedings of the National Academy of Sciences Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells Multidisciplinary |
| author_sort |
breault, david t. |
| spelling |
Breault, David T. Min, Irene M. Carlone, Diana L. Farilla, Loredana G. Ambruzs, Dana M. Henderson, Daniel E. Algra, Selma Montgomery, Robert K. Wagers, Amy J. Hole, Nicholas 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0804800105 <jats:p>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 (<jats:italic>mTert</jats:italic>)-GFP-transgenic mice and assayed the ability of<jats:italic>mTert</jats:italic>-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine.<jats:italic>mTert</jats:italic>-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<jats:italic>mTert</jats:italic>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<jats:sup>+</jats:sup>BM cells showed long-term, serial, multilineage BM reconstitution, fulfilling the functional definition of hematopoietic stem cells. Together, these data provide direct evidence that<jats:italic>mTert</jats:italic>-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.</jats:p> Generation of<i>mTert</i>-GFP mice as a model to identify and study tissue progenitor cells Proceedings of the National Academy of Sciences |
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Proceedings of the National Academy of Sciences, 2008 |
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Proceedings of the National Academy of Sciences, 2008 |
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| title |
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_unstemmed |
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_full |
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_fullStr |
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_full_unstemmed |
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_short |
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_sort |
generation of<i>mtert</i>-gfp mice as a model to identify and study tissue progenitor cells |
| topic |
Multidisciplinary |
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http://dx.doi.org/10.1073/pnas.0804800105 |
| publishDate |
2008 |
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10420-10425 |
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<jats:p>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 (<jats:italic>mTert</jats:italic>)-GFP-transgenic mice and assayed the ability of<jats:italic>mTert</jats:italic>-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine.<jats:italic>mTert</jats:italic>-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<jats:italic>mTert</jats:italic>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<jats:sup>+</jats:sup>BM cells showed long-term, serial, multilineage BM reconstitution, fulfilling the functional definition of hematopoietic stem cells. Together, these data provide direct evidence that<jats:italic>mTert</jats:italic>-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.</jats:p> |
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| author | Breault, David T., Min, Irene M., Carlone, Diana L., Farilla, Loredana G., Ambruzs, Dana M., Henderson, Daniel E., Algra, Selma, Montgomery, Robert K., Wagers, Amy J., Hole, Nicholas |
| author_facet | Breault, David T., Min, Irene M., Carlone, Diana L., Farilla, Loredana G., Ambruzs, Dana M., Henderson, Daniel E., Algra, Selma, Montgomery, Robert K., Wagers, Amy J., Hole, Nicholas, Breault, David T., Min, Irene M., Carlone, Diana L., Farilla, Loredana G., Ambruzs, Dana M., Henderson, Daniel E., Algra, Selma, Montgomery, Robert K., Wagers, Amy J., Hole, Nicholas |
| author_sort | breault, david t. |
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| description | <jats:p>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 (<jats:italic>mTert</jats:italic>)-GFP-transgenic mice and assayed the ability of<jats:italic>mTert</jats:italic>-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine.<jats:italic>mTert</jats:italic>-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<jats:italic>mTert</jats:italic>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<jats:sup>+</jats:sup>BM cells showed long-term, serial, multilineage BM reconstitution, fulfilling the functional definition of hematopoietic stem cells. Together, these data provide direct evidence that<jats:italic>mTert</jats:italic>-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.</jats:p> |
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| imprint | Proceedings of the National Academy of Sciences, 2008 |
| imprint_str_mv | Proceedings of the National Academy of Sciences, 2008 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Rs1, DE-Pl11, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Breault, David T. Min, Irene M. Carlone, Diana L. Farilla, Loredana G. Ambruzs, Dana M. Henderson, Daniel E. Algra, Selma Montgomery, Robert K. Wagers, Amy J. Hole, Nicholas 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0804800105 <jats:p>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 (<jats:italic>mTert</jats:italic>)-GFP-transgenic mice and assayed the ability of<jats:italic>mTert</jats:italic>-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine.<jats:italic>mTert</jats:italic>-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<jats:italic>mTert</jats:italic>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<jats:sup>+</jats:sup>BM cells showed long-term, serial, multilineage BM reconstitution, fulfilling the functional definition of hematopoietic stem cells. Together, these data provide direct evidence that<jats:italic>mTert</jats:italic>-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.</jats:p> Generation of<i>mTert</i>-GFP mice as a model to identify and study tissue progenitor cells Proceedings of the National Academy of Sciences |
| spellingShingle | Breault, David T., Min, Irene M., Carlone, Diana L., Farilla, Loredana G., Ambruzs, Dana M., Henderson, Daniel E., Algra, Selma, Montgomery, Robert K., Wagers, Amy J., Hole, Nicholas, Proceedings of the National Academy of Sciences, Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells, Multidisciplinary |
| title | Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_full | Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_fullStr | Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_full_unstemmed | Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_short | Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| title_sort | generation of<i>mtert</i>-gfp mice as a model to identify and study tissue progenitor cells |
| title_unstemmed | Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.0804800105 |