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Transcriptome analysis of mouse stem cells and early embryos.

Sharov AA, Piao Y, Matoba R, Dudekula DB, Qian Y, VanBuren V, Falco G, Martin PR, Stagg CA, Bassey UC, Wang Y, Carter MG, Hamatani T, Aiba K, Akutsu H, Sharova L, Tanaka TS, Kimber WL, Yoshikawa T, Jaradat SA, Pantano S, Nagaraja R, Boheler KR, Taub D, Hodes RJ, Longo DL, Schlessinger D, Keller J, Klotz E, Kelsoe G, Umezawa A, Vescovi AL, Rossant J, Kunath T, Hogan BL, Curci A, D'Urso M, Kelso J, Hide W, Ko MS - PLoS Biol. (2003)

Bottom Line: Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues.This can be a first step towards a possible definition of a molecular scale of cellular potency.The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine.

View Article: PubMed Central - PubMed

Affiliation: National Institute on Aging, Baltimore, Maryland, USA.

ABSTRACT
Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that include oocytes, blastocysts, and embryonic and adult stem cells, we obtained 249,200 high-quality EST sequences and clustered them with public sequences to produce an index of approximately 30,000 total mouse genes that includes 977 previously unidentified genes. Analysis of gene expression levels by EST frequency identifies genes that characterize preimplantation embryos, embryonic stem cells, and adult stem cells, thus providing potential markers as well as clues to the functional features of these cells. Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues. This can be a first step towards a possible definition of a molecular scale of cellular potency. The sequences and cDNA clones recovered in this work provide a comprehensive resource for genes functioning in early mouse embryos and stem cells. The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine.

Show MeSH
Relationship between PC3 and Average Expression Levels of 88 Signature GenesA list of 88 genes associated with developmental potential: Birc2, Bmp15, Btg4, Cdc25a, Cyp11a, Dtx2, E2f1, Fmn2, Folr4, Gdf9, Krt2–16, Mitc1, Oas1d, Oas1e, Obox3, Prkab1, Rfpl4, Rgs2, Rnf35, Rnpc1, Slc21a11, Spin, Tcl1, Tcl1b1, Tcl1b3, 1810015H18Rik, 2210021E03Rik, 2410003C07Rik, 2610005B21Rik, 2610005H11Rik, 3230401D17Rik, 4833422F24Rik, 4921528E07Rik, 4933428G09Rik, 5730419I09Rik, A030007L17Rik, A930014I12Rik, E130301L11Rik, AA617276, Bcl2l10, MGC32471, MGC38133, MGC38960, D7Ertd784e, and 44 genes with only NIA U numbers (see Dataset S10).
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pbio.0000074-g005: Relationship between PC3 and Average Expression Levels of 88 Signature GenesA list of 88 genes associated with developmental potential: Birc2, Bmp15, Btg4, Cdc25a, Cyp11a, Dtx2, E2f1, Fmn2, Folr4, Gdf9, Krt2–16, Mitc1, Oas1d, Oas1e, Obox3, Prkab1, Rfpl4, Rgs2, Rnf35, Rnpc1, Slc21a11, Spin, Tcl1, Tcl1b1, Tcl1b3, 1810015H18Rik, 2210021E03Rik, 2410003C07Rik, 2610005B21Rik, 2610005H11Rik, 3230401D17Rik, 4833422F24Rik, 4921528E07Rik, 4933428G09Rik, 5730419I09Rik, A030007L17Rik, A930014I12Rik, E130301L11Rik, AA617276, Bcl2l10, MGC32471, MGC38133, MGC38960, D7Ertd784e, and 44 genes with only NIA U numbers (see Dataset S10).

Mentions: To identify a group of genes associated with the PC3 axis, we first fixed the coordinate of each cell type on PC3 and searched for genes whose log-transformed frequencies correlated with this coordinate in each cell type. Correlation analysis combined with the FDR method (FDR = 0.1) revealed 88 genes whose expression levels were significantly associated with PC3 (Dataset S10). To test how well these genes represent PC3, we plotted the sum of log-transformed EST frequencies for these 88 genes versus PC3 projections of the same cell types (Figure 5). Most cells were positioned diagonally relative to the original PC3 coordinates, indicating that the average expression levels of these 88 genes can roughly represent cell type position along the PC3 coordinate. Because the PC3 axis does not have a unit and cannot be directly translated to variables measured by molecular biological techniques, the possible use of 88 genes as a surrogate for the PC3 axis will help to test this working hypothesis in the future.


Transcriptome analysis of mouse stem cells and early embryos.

Sharov AA, Piao Y, Matoba R, Dudekula DB, Qian Y, VanBuren V, Falco G, Martin PR, Stagg CA, Bassey UC, Wang Y, Carter MG, Hamatani T, Aiba K, Akutsu H, Sharova L, Tanaka TS, Kimber WL, Yoshikawa T, Jaradat SA, Pantano S, Nagaraja R, Boheler KR, Taub D, Hodes RJ, Longo DL, Schlessinger D, Keller J, Klotz E, Kelsoe G, Umezawa A, Vescovi AL, Rossant J, Kunath T, Hogan BL, Curci A, D'Urso M, Kelso J, Hide W, Ko MS - PLoS Biol. (2003)

Relationship between PC3 and Average Expression Levels of 88 Signature GenesA list of 88 genes associated with developmental potential: Birc2, Bmp15, Btg4, Cdc25a, Cyp11a, Dtx2, E2f1, Fmn2, Folr4, Gdf9, Krt2–16, Mitc1, Oas1d, Oas1e, Obox3, Prkab1, Rfpl4, Rgs2, Rnf35, Rnpc1, Slc21a11, Spin, Tcl1, Tcl1b1, Tcl1b3, 1810015H18Rik, 2210021E03Rik, 2410003C07Rik, 2610005B21Rik, 2610005H11Rik, 3230401D17Rik, 4833422F24Rik, 4921528E07Rik, 4933428G09Rik, 5730419I09Rik, A030007L17Rik, A930014I12Rik, E130301L11Rik, AA617276, Bcl2l10, MGC32471, MGC38133, MGC38960, D7Ertd784e, and 44 genes with only NIA U numbers (see Dataset S10).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC300684&req=5

pbio.0000074-g005: Relationship between PC3 and Average Expression Levels of 88 Signature GenesA list of 88 genes associated with developmental potential: Birc2, Bmp15, Btg4, Cdc25a, Cyp11a, Dtx2, E2f1, Fmn2, Folr4, Gdf9, Krt2–16, Mitc1, Oas1d, Oas1e, Obox3, Prkab1, Rfpl4, Rgs2, Rnf35, Rnpc1, Slc21a11, Spin, Tcl1, Tcl1b1, Tcl1b3, 1810015H18Rik, 2210021E03Rik, 2410003C07Rik, 2610005B21Rik, 2610005H11Rik, 3230401D17Rik, 4833422F24Rik, 4921528E07Rik, 4933428G09Rik, 5730419I09Rik, A030007L17Rik, A930014I12Rik, E130301L11Rik, AA617276, Bcl2l10, MGC32471, MGC38133, MGC38960, D7Ertd784e, and 44 genes with only NIA U numbers (see Dataset S10).
Mentions: To identify a group of genes associated with the PC3 axis, we first fixed the coordinate of each cell type on PC3 and searched for genes whose log-transformed frequencies correlated with this coordinate in each cell type. Correlation analysis combined with the FDR method (FDR = 0.1) revealed 88 genes whose expression levels were significantly associated with PC3 (Dataset S10). To test how well these genes represent PC3, we plotted the sum of log-transformed EST frequencies for these 88 genes versus PC3 projections of the same cell types (Figure 5). Most cells were positioned diagonally relative to the original PC3 coordinates, indicating that the average expression levels of these 88 genes can roughly represent cell type position along the PC3 coordinate. Because the PC3 axis does not have a unit and cannot be directly translated to variables measured by molecular biological techniques, the possible use of 88 genes as a surrogate for the PC3 axis will help to test this working hypothesis in the future.

Bottom Line: Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues.This can be a first step towards a possible definition of a molecular scale of cellular potency.The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine.

View Article: PubMed Central - PubMed

Affiliation: National Institute on Aging, Baltimore, Maryland, USA.

ABSTRACT
Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that include oocytes, blastocysts, and embryonic and adult stem cells, we obtained 249,200 high-quality EST sequences and clustered them with public sequences to produce an index of approximately 30,000 total mouse genes that includes 977 previously unidentified genes. Analysis of gene expression levels by EST frequency identifies genes that characterize preimplantation embryos, embryonic stem cells, and adult stem cells, thus providing potential markers as well as clues to the functional features of these cells. Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues. This can be a first step towards a possible definition of a molecular scale of cellular potency. The sequences and cDNA clones recovered in this work provide a comprehensive resource for genes functioning in early mouse embryos and stem cells. The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine.

Show MeSH