Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs.
Remarkably, although cardiac disease accounts for the largest proportion of adult mortality and morbidity in the industrialized world, the genetic programs controlling early cardiogenesis are largely incompletely understood. To better understand this process, we set out to identify genes whose expre...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-05-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2364653?pdf=render |
| _version_ | 1811212817373593600 |
|---|---|
| author | Ronald A Miller Nicolas Christoforou Jonathan Pevsner Andrew S McCallion John D Gearhart |
| author_facet | Ronald A Miller Nicolas Christoforou Jonathan Pevsner Andrew S McCallion John D Gearhart |
| author_sort | Ronald A Miller |
| collection | DOAJ |
| description | Remarkably, although cardiac disease accounts for the largest proportion of adult mortality and morbidity in the industrialized world, the genetic programs controlling early cardiogenesis are largely incompletely understood. To better understand this process, we set out to identify genes whose expression is enriched within early cardiac fated populations, obtaining the transcriptional signatures of mouse embryonic stem cells (mESCs) at defined intervals during their differentiation along a cardiac path. We compared the RNA profiles of cardiac precursors cells (CPCs) with time-matched non-CPCs and undifferentiated mESCs, using a transgenic mESC line harboring an Nkx2-5 cardiac-specific regulatory sequence driving green fluorescent protein (GFP) to facilitate selection of CPCs. We identify 176 transcripts that are significantly elevated in their abundance within CPCs compared with other assayed populations, predicting that they will likely play a role in cardiogenesis. Of note, approximately 24% (43/176) of the cardiogenic candidate transcripts have known roles in cardiac function or development. Importantly, we evaluated the biological relevance of a significant subset 31/133 (23%) of the remaining candidate genes by in situ hybridization at multiple time points during development (embryonic day, E7.5-9.5) and report that all were expressed in key cardiac structures during cardiogenesis. Furthermore 9/31, of which many were previously uncharacterized, were detected as early as the formation of the cardiac crescent. These data demonstrate the potential power of integrating genomic approaches with mESC differentiation to illuminate developmental processes, and provides a valuable resource that may be mined to further elucidate the genetic programs underlying cardiogenesis. |
| first_indexed | 2024-04-12T05:35:36Z |
| format | Article |
| id | doaj.art-68c643f4174e43e38b849bfb7d0ade42 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:35:36Z |
| publishDate | 2008-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-68c643f4174e43e38b849bfb7d0ade422022-12-22T03:45:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-05-0135e217610.1371/journal.pone.0002176Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs.Ronald A MillerNicolas ChristoforouJonathan PevsnerAndrew S McCallionJohn D GearhartRemarkably, although cardiac disease accounts for the largest proportion of adult mortality and morbidity in the industrialized world, the genetic programs controlling early cardiogenesis are largely incompletely understood. To better understand this process, we set out to identify genes whose expression is enriched within early cardiac fated populations, obtaining the transcriptional signatures of mouse embryonic stem cells (mESCs) at defined intervals during their differentiation along a cardiac path. We compared the RNA profiles of cardiac precursors cells (CPCs) with time-matched non-CPCs and undifferentiated mESCs, using a transgenic mESC line harboring an Nkx2-5 cardiac-specific regulatory sequence driving green fluorescent protein (GFP) to facilitate selection of CPCs. We identify 176 transcripts that are significantly elevated in their abundance within CPCs compared with other assayed populations, predicting that they will likely play a role in cardiogenesis. Of note, approximately 24% (43/176) of the cardiogenic candidate transcripts have known roles in cardiac function or development. Importantly, we evaluated the biological relevance of a significant subset 31/133 (23%) of the remaining candidate genes by in situ hybridization at multiple time points during development (embryonic day, E7.5-9.5) and report that all were expressed in key cardiac structures during cardiogenesis. Furthermore 9/31, of which many were previously uncharacterized, were detected as early as the formation of the cardiac crescent. These data demonstrate the potential power of integrating genomic approaches with mESC differentiation to illuminate developmental processes, and provides a valuable resource that may be mined to further elucidate the genetic programs underlying cardiogenesis.http://europepmc.org/articles/PMC2364653?pdf=render |
| spellingShingle | Ronald A Miller Nicolas Christoforou Jonathan Pevsner Andrew S McCallion John D Gearhart Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. PLoS ONE |
| title | Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. |
| title_full | Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. |
| title_fullStr | Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. |
| title_full_unstemmed | Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. |
| title_short | Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. |
| title_sort | efficient array based identification of novel cardiac genes through differentiation of mouse escs |
| url | http://europepmc.org/articles/PMC2364653?pdf=render |
| work_keys_str_mv | AT ronaldamiller efficientarraybasedidentificationofnovelcardiacgenesthroughdifferentiationofmouseescs AT nicolaschristoforou efficientarraybasedidentificationofnovelcardiacgenesthroughdifferentiationofmouseescs AT jonathanpevsner efficientarraybasedidentificationofnovelcardiacgenesthroughdifferentiationofmouseescs AT andrewsmccallion efficientarraybasedidentificationofnovelcardiacgenesthroughdifferentiationofmouseescs AT johndgearhart efficientarraybasedidentificationofnovelcardiacgenesthroughdifferentiationofmouseescs |