"Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells
Tóm tắt
The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells. A total of 216 genes are enriched in all three types of stem cells, and several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes (represented by expressed sequence tags) whose functions are unknown. Embryonic and neural stem cells have many similarities at the transcriptional level. These results provide a foundation for a more detailed understanding of stem cell biology.
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Tài liệu tham khảo
Y. Jiang et al. Nature advance online publication 20 June 2002 (10.1038/nature00870).
See supporting data on Science Online.
research___ Genome Biol. 2 0032.1 (2001).
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M. Ramalho-Santos S. Yoon Y. Matsuzaki R. C. Mulligan D. A. Melton data not shown.
Given that ESCs and NSCs are selected as cells engaged in the cell cycle whereas HSCs are thought to be predominantly quiescent ( 37 38 ) one would expect the ESC/NSC overlap (relative to the ESC/HSC overlap) to be enriched for genes with cell cycle functions. However this is not the case: 11.7% of genes overlapping between ESCs and NSCs contain the annotation “cell cycle ” whereas that number is 13.1% in the ESC/HSC overlap ( 12 ). In fact this high ESC/NSC overlap is not biased for genes containing other Gene Ontology annotations such as “growth ” “nucleus/nucleic ” “cell communication ” “metabolism ” or “stress/response ” and only minor biases can be detected in the categories “cytoplasm” and “chaperone” ( 12 ). It is unlikely that the preferential overlap between ESCs and NSCs has to do with the fact that both are cultured in vitro because ESCs and NSCs are grown in very different conditions: ESCs attached to fibroblast feeders in serum and NSCs in floating clusters without serum ( 12 ). Moreover the ESC/NSC overlap is very extensive including more than 60% of ESC-enriched genes.
We thank M. C. Kao and W. Wong for calculating the P value for the enrichment of chromosome 17 for SC-enriched genes. We thank C. Stewart for C57Bl/6 ESC and the following people for advice: S. Kume (ESC culture) F. Doetsch (NSC culture) R. Baugh (mRNA amplification) J. Couget (array hybridization) and C. Li and W. Wong (dChip software). We thank W. Wong N. Benvenisty F. Doetsch R. Baugh S. Haggarty E. Lammert D. Cavalieri and C. Annerén for critical reading of the manuscript. M.R.-S. was supported in part by a predoctoral fellowship from the Foundation for Science and Technology Portugal and dedicates this article to the memory of Francisco Varela (1946–2001) neuroscientist theoretical biologist and co-author of the concept of “autopoiesis ” an inspiration for this work. Research was supported by NIH grants R24 DK56947 (D.A.M.) and P60 HL54785 (R.C.M.) and in part by a grant from Amgen (R.C.M.); R.C.M. is an equity-holding consultant for Amgen; D.A.M. is an investigator of the HHMI. Inquiries regarding HSC purification should be addressed to R.C.M. ([email protected]).