Gene function in early mouse embryonic stem cell differentiation
<p>Abstract</p> <p>Background</p> <p>Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2007-03-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/8/85 |
| _version_ | 1818002196607795200 |
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| author | Campbell Pearl A Muro Enrique M Perez-Iratxeta Carolina Palidwor Gareth Porter Christopher J Sene Kagnew Rudnicki Michael A Andrade-Navarro Miguel A |
| author_facet | Campbell Pearl A Muro Enrique M Perez-Iratxeta Carolina Palidwor Gareth Porter Christopher J Sene Kagnew Rudnicki Michael A Andrade-Navarro Miguel A |
| author_sort | Campbell Pearl A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks.</p> <p>Results</p> <p>We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. <it>Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1</it>), our analysis points to others (such as transcription factor <it>Phf21a</it>, extracellular matrix related <it>Lama1 </it>and <it>Cyr61</it>, or endoplasmic reticulum related <it>Sc4mol </it>and <it>Scd2</it>) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set.</p> <p>Conclusion</p> <p>Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and identifies a functional and phylogenetic signature for the genes involved. The data generated constitute a valuable resource for further studies. All DNA microarray data used in this study are available in the StemBase database of stem cell gene expression data <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and in the NCBI's GEO database.</p> |
| first_indexed | 2024-04-14T03:42:35Z |
| format | Article |
| id | doaj.art-b58bac1fa3bf4e529dab99fd674d9b99 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-14T03:42:35Z |
| publishDate | 2007-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-b58bac1fa3bf4e529dab99fd674d9b992022-12-22T02:14:27ZengBMCBMC Genomics1471-21642007-03-01818510.1186/1471-2164-8-85Gene function in early mouse embryonic stem cell differentiationCampbell Pearl AMuro Enrique MPerez-Iratxeta CarolinaPalidwor GarethPorter Christopher JSene KagnewRudnicki Michael AAndrade-Navarro Miguel A<p>Abstract</p> <p>Background</p> <p>Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks.</p> <p>Results</p> <p>We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. <it>Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1</it>), our analysis points to others (such as transcription factor <it>Phf21a</it>, extracellular matrix related <it>Lama1 </it>and <it>Cyr61</it>, or endoplasmic reticulum related <it>Sc4mol </it>and <it>Scd2</it>) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set.</p> <p>Conclusion</p> <p>Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and identifies a functional and phylogenetic signature for the genes involved. The data generated constitute a valuable resource for further studies. All DNA microarray data used in this study are available in the StemBase database of stem cell gene expression data <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and in the NCBI's GEO database.</p>http://www.biomedcentral.com/1471-2164/8/85 |
| spellingShingle | Campbell Pearl A Muro Enrique M Perez-Iratxeta Carolina Palidwor Gareth Porter Christopher J Sene Kagnew Rudnicki Michael A Andrade-Navarro Miguel A Gene function in early mouse embryonic stem cell differentiation BMC Genomics |
| title | Gene function in early mouse embryonic stem cell differentiation |
| title_full | Gene function in early mouse embryonic stem cell differentiation |
| title_fullStr | Gene function in early mouse embryonic stem cell differentiation |
| title_full_unstemmed | Gene function in early mouse embryonic stem cell differentiation |
| title_short | Gene function in early mouse embryonic stem cell differentiation |
| title_sort | gene function in early mouse embryonic stem cell differentiation |
| url | http://www.biomedcentral.com/1471-2164/8/85 |
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