Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold wit...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2014
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| Online Access: | http://hdl.handle.net/1721.1/85578 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-8855-8647 https://orcid.org/0000-0001-8353-9316 |
| _version_ | 1810980627391971328 |
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| author | Gurtan, Allan M. Ravi, Arvind Bosson, Andrew David JnBaptiste, Courtney Kenneil Bhutkar, Arjun (AJ) Whittaker, Charles A. Young, Richard A. Sharp, Phillip A. Rahl, Peter B. |
| author2 | Whitaker College of Health Sciences and Technology |
| author_facet | Whitaker College of Health Sciences and Technology Gurtan, Allan M. Ravi, Arvind Bosson, Andrew David JnBaptiste, Courtney Kenneil Bhutkar, Arjun (AJ) Whittaker, Charles A. Young, Richard A. Sharp, Phillip A. Rahl, Peter B. |
| author_sort | Gurtan, Allan M. |
| collection | MIT |
| description | MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function. |
| first_indexed | 2024-09-23T10:01:51Z |
| format | Article |
| id | mit-1721.1/85578 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:01:51Z |
| publishDate | 2014 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/855782022-09-26T15:16:11Z Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts Gurtan, Allan M. Ravi, Arvind Bosson, Andrew David JnBaptiste, Courtney Kenneil Bhutkar, Arjun (AJ) Whittaker, Charles A. Young, Richard A. Sharp, Phillip A. Rahl, Peter B. Whitaker College of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Gurtan, Allan M. Ravi, Arvind Bosson, Andrew David JnBaptiste, Courtney Kenneil Bhutkar, Arjun (AJ) Whittaker, Charles A. Young, Richard A. Sharp, Phillip A. MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function. National Institutes of Health (U.S.) (Grant RO1-GM34277) National Cancer Institute (U.S.) (Grant PO1-CA42063) National Institutes of Health (U.S.) (Grant RO1-HG002668) National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051) Leukemia & Lymphoma Society of America (Grant 5198-09) 2014-03-10T17:02:48Z 2014-03-10T17:02:48Z 2013-04 2013-02 Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 http://hdl.handle.net/1721.1/85578 Gurtan, A. M., A. Ravi, P. B. Rahl, A. D. Bosson, C. K. JnBaptiste, A. Bhutkar, C. A. Whittaker, R. A. Young, and P. A. Sharp. “Let-7 Represses Nr6a1 and a Mid-Gestation Developmental Program in Adult Fibroblasts.” Genes & Development 27, no. 8 (April 15, 2013): 941–954. Copyright © 2013 by Cold Spring Harbor Laboratory Press https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-8855-8647 https://orcid.org/0000-0001-8353-9316 en_US http://dx.doi.org/10.1101/gad.215376.113 Genes & Development Creative Commons Attribution‐NonCommercial License http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Press Genes and Development |
| spellingShingle | Gurtan, Allan M. Ravi, Arvind Bosson, Andrew David JnBaptiste, Courtney Kenneil Bhutkar, Arjun (AJ) Whittaker, Charles A. Young, Richard A. Sharp, Phillip A. Rahl, Peter B. Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts |
| title | Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts |
| title_full | Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts |
| title_fullStr | Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts |
| title_full_unstemmed | Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts |
| title_short | Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts |
| title_sort | let 7 represses nr6a1 and a mid gestation developmental program in adult fibroblasts |
| url | http://hdl.handle.net/1721.1/85578 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-8855-8647 https://orcid.org/0000-0001-8353-9316 |
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