Miguel Ramalho-Santos, PhD, MScRegulation of Stem Cell Pluripotency and Reprogramming |
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Selected Publications | Complete Publications
Embryonic Stem (ES) cells have the remarkable ability to give rise to all cell types of the body, and for this reason they are called pluripotent. Because of their pluripotency, ES cells provide exciting new avenues in Regenerative Medicine. ES cells may allow us to understand cellular differentiation in normal and diseased states. ES cells may also in the future be used to generate particular cell types that are needed by patients.
My lab is interested in the genetic regulation of pluripotency. We aim to answer the question of how such broad differentiation potential is maintained at the molecular level in pluripotent cells of the mammalian embryo and in ES cells in culture. We have characterized the gene expression profiles of pluripotent cells and identified a transcriptional program that is required to maintain pluripotency. We are dissecting the transcriptional regulatory networks of pluripotency. We are addressing the question of the in vivo significance of pluripotency, which our data indicate is closely associated with germline development in mammals. In parallel, we are investigating the mechanisms that underlie reprogramming of non-pluripotent cells to the pluripotent state. We use techniques such as mouse genetics and embryology, microarrays, bioinformatics, mouse and human ES cell manipulation and RNA interference. Understanding the regulation of stem cell pluripotency will provide basic insights into development of the early mammalian embryo and the germline, and will inform efforts to generate patient-specific pluripotent stem cells and rationally tailor their differentiation towards cells of therapeutic interest.
Selected Publications
Ramalho-Santos M, Melton DA, and McMahon AP. (2000) Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127:2763-2772.
Zhang XM, Ramalho-Santos M, and McMahon AP. (2001) Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell 105:781-792.
Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, and Melton DA. (2002) ‘Stemness’: transcriptional profiling of embryonic and adult stem cells. Science 298:597-600.
Ramalho-Santos M. (2004) Stem cells as probabilistic self-producing entities. Bioessays 26:1013-1016.
Heidersbach A, Gaspar-Maia A, McManus M, and Ramalho-Santos M. (2006) RNA interference in embryonic stem cells and the prospects for future therapies. Gene Therapy 13:478-86.
Ramalho-Santos M and Willenbring H. (2007) On the origin of the term ‘stem cell’. Cell Stem Cell 1: 35-38.
Grskovic M, Chaivorapol C, Gaspar-Maia A, Li H, and Ramalho-Santos M. (2007) Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells. PLoS Genetics 3:1524-1540.
Blelloch R, Venere M, Yen J, and Ramalho-Santos M*. (2007) Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell 1: 245-247.
Wong C1, Gaspar-Maia A, Ramalho-Santos M1*, and Reijo Pera R*. (2008) High-efficiency stem cell fusion-mediated assay reveals Sall4 as an enhancer of reprogramming. PLoS ONE 3(4):e1955.
Wei G, Yeh RF, Hebrok M, Ramalho-Santos M*. (2008) Maintenance of the transcriptional program for pluripotency in the embryonic germline: implications for reprogramming and tumorigenesis. [submitted]
* - corresponding author
1 - equal contribution
