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Typus
Verschleierung
Bearbeiter
Hindemith
Gesichtet
Yes.png
Untersuchte Arbeit:
Seite: 20, Zeilen: 14-27
Quelle: Bryder_et_al_2006
Seite(n): 341, Zeilen: r.col: 11-25, 28-37
HSCs express a great diversity of transcripts, including a wide range of genes originally believed to be restricted to more mature and lineage-committed cell types. The single-cell polymerase chain reaction strategies had suggested that such loose transcription of lineage-associated transcripts was necessary to prime primitive progenitor cells for differentiation toward downstream fates.63

An alternative interpretation is that stem cells possess global transcriptional accessibility and that it is the step-wise restriction of locus accessibility that underlies lineage specification.64,65 Cell fate can also be switched from one committed cell type to another on over expression of IL2R or GM-CSF receptors 17,18 GATA-166 or C/EBP /ß [sic] .67 An additional mechanism of lineage specification has been revealed which attributes to the ablation of the transcription factors Pax5 or GATA-1 in lineage-restricted progenitors. This was sufficient to despecify their B-cell and erythroid fate, respectively, and allow a multilineage developmental potential.


17. Kondo M, Scherer DC, Miyamoto T, et al. Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature. 2000;407:383-386.

18. Kondo M, Wagers AJ, Manz MG, et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol. 2003;21:759-806.

63. Mikkola HK, Fujiwara Y, Schlaeger TM, Traver D, Orkin SH. Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood. 2003;101:508-516.

64. Akashi K, Reya T, Dalma-Weiszhausz D, Weissman IL. Lymphoid precursors. Curr Opin Immunol. 2000;12:144-150.

65. Akashi K, He X, Chen J, et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood. 2003;101:383- 389.

66. Iwasaki H, Mizuno S, Wells RA, Cantor AB, Watanabe S, Akashi K. GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity. 2003;19:451-462.

67. Xie H, Ye M, Feng R, Graf T. Stepwise reprogramming of B cells into macrophages. Cell. 2004;117:663-676.

One surprising finding of these studies is the discovery that HSCs express a great diversity of transcripts, including a wide range of genes originally believed to be restricted to more mature and lineage-committed cell types. The findings of these genome-wide expression studies had in fact been foreshadowed by earlier studies using single-cell polymerase chain reaction strategies that had suggested that such promiscuous transcription of lineage-associated transcripts was necessary to prime primitive progenitor cells for differentiation toward downstream fates.39,40 An alternative interpretation posits that stem cells possess global transcriptional accessibility and that it is the step-wise restriction of locus accessibility that underlies lineage specification.37 [...] This has been exemplified in experiments in which cell fate was switched from one committed cell type to another on overexpression of IL2R or GM-CSF receptors,41 GATA-1,42 or C/EBPα/β.43 An additional mechanism of lineage specification was revealed in experiments in which ablation of the transcription factors Pax5 or GATA-1 in lineage-restricted progenitors was found to be sufficient to despecify their B-cell and erythroid fate, respectively, and allow a multilineage developmental potential.44,45

37. Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J, Li L: Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood 2003, 101:383–389

39. Miyamoto T, Iwasaki H, Reizis B, Ye M, Graf T, Weissman IL, Akashi K: Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell 2002, 3:137–147

40. Hu M, Krause D, Greaves M, Sharkis S, Dexter M, Heyworth C, Enver T: Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev 1997, 11:774–785

41. Kondo M, Scherer DC, Miyamoto T, King AG, Akashi K, Sugamura K, Weissman IL: Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature 2000, 407:383–386

42. Iwasaki H, Mizuno S, Wells RA, Cantor AB, Watanabe S, Akashi K: GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity 2003, 19:451–462

43. Xie H, Ye M, Feng R, Graf T: Stepwise reprogramming of B cells into macrophages. Cell 2004, 117:663–676

44. Mikkola I, Heavey B, Horcher M, Busslinger M: Reversion of B cell commitment upon loss of Pax5 expression. Science 2002, 297:110–113

45. Kitajima K, Zheng J, Yen H, Sugiyama D, Nakano T: Multipotential differentiation ability of GATA-1-null erythroid-committed cells. Genes Dev 2006, 20:654–659

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