Deneault Eric, Cellot Sonia, Faubert Amélie, Laverdure Jean-Philippe, Fréchette Mélanie, Chagraoui Jalila, Mayotte Nadine, Sauvageau Martin, Ting Stephen B, Sauvageau Guy
Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, Quebec H3C 3J7, Canada.
Cell. 2009 Apr 17;137(2):369-79. doi: 10.1016/j.cell.2009.03.026.
Despite tremendous progress made toward the identification of the molecular circuitry that governs cell fate in embryonic stem cells, genes controlling this process in the adult hematopoietic stem cell have proven to be more difficult to unmask. We now report the results of a novel gain-of-function screening approach, which identified a series of 18 nuclear factors that affect hematopoietic stem cell activity. Overexpression of ten of these factors resulted in an increased repopulating activity compared to unmanipulated cells. Interestingly, at least four of the 18 factors, Fos, Tcfec, Hmgb1, and Sfpi1, show non-cell-autonomous functions. The utilization of this screening method together with the creation of a database enriched for potential determinants of hematopoietic stem cell self-renewal will serve as a resource to uncover regulatory networks in these cells.
尽管在识别控制胚胎干细胞命运的分子回路方面取得了巨大进展，但事实证明，揭示控制成体造血干细胞这一过程的基因更加困难。我们现在报告一种新型功能获得性筛选方法的结果，该方法鉴定出一系列影响造血干细胞活性的18种核因子。与未处理的细胞相比，其中10种因子的过表达导致了重建造血活性的增加。有趣的是，18种因子中的至少4种，即Fos、Tcfec、Hmgb1和Sfpi1，表现出非细胞自主功能。这种筛选方法的应用以及创建一个富含造血干细胞自我更新潜在决定因素的数据库，将成为揭示这些细胞调控网络的资源。
