Date Published: December 22, 2003
Publisher: Public Library of Science
Author(s): Alexei A Sharov, Yulan Piao, Ryo Matoba, Dawood B Dudekula, Yong Qian, Vincent VanBuren, Geppino Falco, Patrick R Martin, Carole A Stagg, Uwem C Bassey, Yuxia Wang, Mark G Carter, Toshio Hamatani, Kazuhiro Aiba, Hidenori Akutsu, Lioudmila Sharova, Tetsuya S Tanaka, Wendy L Kimber, Toshiyuki Yoshikawa, Saied A Jaradat, Serafino Pantano, Ramaiah Nagaraja, Kenneth R Boheler, Dennis Taub, Richard J Hodes, Dan L Longo, David Schlessinger, Jonathan Keller, Emily Klotz, Garnett Kelsoe, Akihiro Umezawa, Angelo L Vescovi, Janet Rossant, Tilo Kunath, Brigid L. M Hogan, Anna Curci, Michele D’Urso, Janet Kelso, Winston Hide, Minoru S. H Ko
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.
Partial Text: With the derivation of pluripotent human embryonic stem (ES) (Thomson et al. 1998) and embryonic germ (EG) (Shamblott et al. 1998) cells that can differentiate into many different cell types, excitement has increased for the prospect of replacing dysfunctional or failing cells and organs. Very little is known, however, about critical molecular mechanisms that can harness or manipulate the potential of cells to foster therapeutic applications targeted to specific tissues.
The sequence information and cDNA clones collected in this work provide the most comprehensive database and resources for genes functioning in early mouse embryos and stem cells. All cDNA clones developed in this project have been made available through the American Type Culture Collection (ATCC). The subset of these cDNA clones have been rearrayed into the condensed clone sets, the NIA Mouse 15K cDNA Clone Set (Tanaka et al. 2000; Kargul et al. 2001) and the 7.4K cDNA Clone Set (VanBuren et al. 2002), which have been made available through designated academic distribution centers. Many genes that are uniquely or predominantly expressed in mouse early embryos and stem cells have been recently incorporated into a 60mer oligonucleotide microarray (Carter et al. 2003). Sequence information has been made available at public sequence databases (e.g., dbEST [Boguski et al. 1993]). Finally, all the information discussed here, as well as the graphical interfaces of the Mouse Gene Index, is available on our Web site at http://lgsun.grc.nia.nih.gov/cDNA/cDNA.html.
To view this Supporting Information with dynamic Web links, see http://lgsun.grc.nia.nih.gov/Supplemental-Information/.