The nature of stem cells: state rather than entity

Stem cells are endowed with self-renewal and multipotential differentiation capacities. Contrary to the expectation that stem cells would selectively express specific genes, these cells have a highly promiscuous gene-expression pattern. Here, I suggest that the transient stem cell state, termed the 'stem state', may be assumed by any cell and that the search for specific genes expressed by all stem cells, which would characterize the stem cell as a cell type, might be futile.

[1]  Peter G. Schultz,et al.  Synthetic small molecules that control stem cell fate , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Ruth Chadwick,et al.  Solidarity and equity: new ethical frameworks for genetic databases , 2001, Nature Reviews Genetics.

[3]  U. Suter,et al.  Instructive Role of Wnt/ß-Catenin in Sensory Fate Specification in Neural Crest Stem Cells , 2004, Science.

[4]  G C Overton,et al.  The genetic program of hematopoietic stem cells. , 2000, Science.

[5]  I. Weissman,et al.  A role for Wnt signalling in self-renewal of haematopoietic stem cells , 2003, Nature.

[6]  S. Karlsson,et al.  Hoxb 4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells , 2004 .

[7]  M. Goumans,et al.  TGF-beta signaling-deficient hematopoietic stem cells have normal self-renewal and regenerative ability in vivo despite increased proliferative capacity in vitro. , 2003, Blood.

[8]  Michael J Green,et al.  Genetic Exceptionalism in Medicine: Clarifying the Differences between Genetic and Nongenetic Tests , 2003, Annals of Internal Medicine.

[9]  E. Tanaka,et al.  Regeneration If They Can Do It, Why Can't We? , 2003, Cell.

[10]  I. Weissman,et al.  The purification and characterization of fetal liver hematopoietic stem cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Greengard,et al.  Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor , 2004, Nature Medicine.

[12]  D. Zipori Regulation of hemopoiesis by cytokines that restrict options for growth and differentiation. , 1990, Cancer cells.

[13]  H. Greely Informed consent and other ethical issues in human population genetics. , 2001, Annual review of genetics.

[14]  J. Bovenberg Should companies set up databases in Europe? , 2000, Nature Biotechnology.

[15]  Anne Cambon-Thomsen,et al.  Assessing the impact of biobanks , 2003, Nature Genetics.

[16]  S. Elledge,et al.  Dicer is essential for mouse development , 2003, Nature Genetics.

[17]  Philip M. Long,et al.  Comment on " 'Stemness': Transcriptional Profiling of Embryonic and Adult Stem Cells" and "A Stem Cell Molecular Signature" (I) , 2003, Science.

[18]  M. Harkin The Devil, The Details, and the HGDP , 1999, Politics and the life sciences.

[19]  D. Nelkin,et al.  Homo economicus: commercialization of body tissue in the age of biotechnology. , 1998, The Hastings Center report.

[20]  A. Kiger,et al.  Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell Cue , 2001, Science.

[21]  U. Schepers A Stem Cell Molecular Signature: Are There Hallmark Properties That are Shared by all Stem Cells? , 2003, Chembiochem : a European journal of chemical biology.

[22]  H. Okano,et al.  Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. , 2004, Immunity.

[23]  M. Feldman,et al.  Proposed model ethical protocol for collecting DNA samples. , 1997, Houston law review.

[24]  A. Dierich,et al.  PU.1 determines the self-renewal capacity of erythroid progenitor cells. , 2004, Blood.

[25]  J. McCarthy,et al.  Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary , 2004, Development.

[26]  M Ramalho Santos STEMNESS: TRANSCRIPTIONAL PROFILING OF EMBRYONIC AND ADULT STEM CELLS , 2002 .

[27]  T. Kitamura,et al.  A stromal cell–derived membrane protein that supports hematopoietic stem cells , 2003, Nature Immunology.

[28]  Z. Grossman,et al.  HIV-1 Viremia Prevents the Establishment of Interleukin 2–producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity , 2003, The Journal of experimental medicine.

[29]  R. Alon,et al.  The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. , 2000, Blood.

[30]  G. Prindull,et al.  Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm. , 2004, Blood.

[31]  R. J. Blatt,et al.  Banking Biological Collections: Data Warehousing, Data Mining, and Data Dilemmas in Genomics and Global Health Policy , 2001, Public Health Genomics.

[32]  M R Anderlik,et al.  Privacy and confidentiality of genetic information: what rules for the new science? , 2001, Annual review of genomics and human genetics.

[33]  A. Evsikov,et al.  Comment on " 'Stemness': Transcriptional Profiling of Embryonic and Adult Stem Cells" and "A Stem Cell Molecular Signature" (II) , 2003, Science.

[34]  I. Black,et al.  Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis , 2002, Journal of neuroscience research.

[35]  Francis S. Collins,et al.  The case for a US prospective cohort study of genes and environment , 2004, Nature.

[36]  E. Emanuel,et al.  The debate over research on stored biological samples: what do sources think? , 2002, Archives of internal medicine.

[37]  G. Grafi How cells dedifferentiate: a lesson from plants. , 2004, Developmental biology.

[38]  C. Bever,et al.  Hematopoietic progenitors express neural genes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. Karlsson,et al.  Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. , 2004, Blood.

[40]  M. Deschênes,et al.  Human genetic research, DNA banking and consent: a question of ‘form’? , 2001, Clinical genetics.

[41]  Douglas A Lauffenburger,et al.  Multivariate proteomic analysis of murine embryonic stem cell self-renewal versus differentiation signaling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[42]  H. Snoeck,et al.  Quantitative Trait Analysis Reveals Transforming Growth Factor-β2 as a Positive Regulator of Early Hematopoietic Progenitor and Stem Cell Function , 2004, The Journal of experimental medicine.

[43]  D. Zipori The renewal and differentiation of hemopoietic stem cells , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[44]  Bartha Maria Knoppers,et al.  Population Genetics and Benefit Sharing , 2001, Public Health Genomics.

[45]  N. Ferrara,et al.  VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism , 2002, Nature.

[46]  Catherine M. Verfaillie,et al.  Pluripotency of mesenchymal stem cells derived from adult marrow , 2002, Nature.

[47]  E. Huberman,et al.  A human peripheral blood monocyte-derived subset acts as pluripotent stem cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[48]  E. Matunis,et al.  Control of Stem Cell Self-Renewal in Drosophila Spermatogenesis by JAK-STAT Signaling , 2001, Science.

[49]  C. Melief,et al.  Adhesion of T and B lymphocytes to extracellular matrix and endothelial cells can be regulated through the beta subunit of VLA , 1992, The Journal of cell biology.

[50]  S. Nishikawa,et al.  Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors. , 1998, Development.

[51]  I. Weissman,et al.  Wnt proteins are lipid-modified and can act as stem cell growth factors , 2003, Nature.

[52]  K. Hoeyer ‘Science is really needed—that’s all I know': informed consent and the non-verbal practices of collecting blood for genetic research in northern Sweden , 2003, New genetics and society.

[53]  R. Moon,et al.  Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[54]  S. Nishikawa,et al.  Dominant role of the niche in melanocyte stem-cell fate determination , 2002, Nature.

[55]  M. Lock Interrogating the Human Diversity Genome Project. , 1994, Social science & medicine.

[56]  S. Kato,et al.  FGF10 maintains stem cell compartment in developing mouse incisors. , 2002, Development.

[57]  Detlef Weigel,et al.  Stem cells that make stems , 2002, Nature.

[58]  R. Jaenisch,et al.  Monoclonal mice generated by nuclear transfer from mature B and T donor cells , 2002, Nature.

[59]  E. Dupin,et al.  Self-renewal capacity is a widespread property of various types of neural crest precursor cells. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[60]  E. Vellenga,et al.  In vitro generation of long-term repopulating hematopoietic stem cells by fibroblast growth factor-1. , 2003, Developmental cell.

[61]  E. Clayton,et al.  Whose DNA is it anyway? Relationships between families and researchers. , 1993, American journal of medical genetics.

[62]  G. Sauvageau,et al.  Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells , 2003, Nature.

[63]  J. Dick,et al.  Rapid myeloerythroid repopulation after intrafemoral transplantation of NOD-SCID mice reveals a new class of human stem cells , 2003, Nature Medicine.

[64]  L. Karlsson,et al.  Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. , 2004, Blood.

[65]  Y. Shav-Tal,et al.  The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control , 2002, Oncogene.

[66]  Irving L. Weissman,et al.  Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells , 2003, Nature.