Transcriptome Analysis Identifies Regulators of Hematopoietic Stem and Progenitor Cells

被引:82
作者
Gazit, Roi [1 ,2 ,8 ]
Garrison, Brian S. [1 ,2 ]
Rao, Tata Nageswara [2 ,3 ]
Shay, Tal [4 ]
Costello, James [5 ]
Ericson, Jeff [6 ]
Kim, Francis [2 ,3 ]
Collins, James J. [5 ,7 ]
Regev, Aviv [4 ,7 ]
Wagers, Amy J. [2 ,3 ,7 ]
Rossi, Derrick J. [1 ,2 ]
机构
[1] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA
[2] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[3] Joslin Diabet Ctr, Boston, MA 02215 USA
[4] Broad Inst, Cambridge, MA 02142 USA
[5] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA
[7] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[8] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol Immunol & Genet, IL-84105 Beer Sheva, Israel
关键词
GENE-EXPRESSION; SELF-RENEWAL; BLOOD; QUIESCENCE; MIGRATION; MARROW; PROLIFERATION; MOBILIZATION; LINEAGE; FUSION;
D O I
10.1016/j.stemcr.2013.07.004
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
Hematopoietic stem cells (HSCs) maintain blood homeostasis and are the functional units of bone marrow transplantation. To improve the molecular understanding of HSCs and their proximal progenitors, we performed transcriptome analysis within the context of the ImmGen Consortium data set. Gene sets that define steady-state and mobilized HSCs, as well as hematopoietic stem and progenitor cells (HSPCs), were determined. Genes involved in transcriptional regulation, including a group of putative transcriptional repressors, were identified in multipotent progenitors and HSCs. Proximal promoter analyses combined with ImmGen module analysis identified candidate regulators of HSCs. Enforced expression of one predicted regulator, Hlf, in diverse HSPC subsets led to extensive self-renewal activity ex vivo. These analyses reveal unique insights into the mechanisms that control the core properties of HSPCs.
引用
收藏
页码:266 / 280
页数:15
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