MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output

被引：227

作者：

O'Connell, Ryan M. ^{[1
]}

Chaudhuri, Aadel A. ^{[1
]}

Rao, Dinesh S. ^{[1
,2
]}

Gibson, William S. J. ^{[1
]}

Balazs, Alejandro B. ^{[1
]}

Baltimore, David ^{[1
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 32期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

cancer; inflammation; myeloid; xenograft; noncoding RNA; ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL; LINEAGE CHOICE; IMMUNE-SYSTEM; PROLIFERATION; EXPRESSION; DICER; ABSENCE; MICE;

D O I：

10.1073/pnas.1009798107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output.

引用

收藏

页码：14235 / 14240

页数：6

相关论文

共 31 条

[1] Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow [J].

Balazs, AB ;

Fabian, AJ ;

Esmon, CT ;

Mulligan, RC .

BLOOD, 2006, 107 (06) :2317-2321

[2] Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs [J].

Bartel, DP ;

Chen, CZ .

NATURE REVIEWS GENETICS, 2004, 5 (05) :396-400

[3] Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation [J].

Bousquet, Marina ;

Quelen, Cathy ;

Rosati, Roberto ;

Mansat-De Mas, Ronique ;

La Starza, Roberta ;

Bastard, Christian ;

Lippert, Eric ;

Talmant, Pascaline ;

Lafage-Pochitaloff, Marina ;

Leroux, Dominique ;

Gervais, Carine ;

Viguie, Franck ;

Lai, Jean-Luc ;

Terre, Christine ;

Beverlo, Berna ;

Sambani, Costantina ;

Hagemeijer, Anne ;

Marynen, Peter ;

Delsol, Georges ;

Dastugue, Nicole ;

Mecucci, Cristina ;

Brousset, Pierre .

JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (11) :2499-2506

[4] Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].

Calin, GA ;

Dumitru, CD ;

Shimizu, M ;

Bichi, R ;

Zupo, S ;

Noch, E ;

Aldler, H ;

Rattan, S ;

Keating, M ;

Rai, K ;

Rassenti, L ;

Kipps, T ;

Negrini, M ;

Bullrich, F ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529

[5] Differential expression of specific microRNA and their targets in acute myeloid leukemia [J].

Cammarata, Giuseppe ;

Augugliaro, Luigi ;

Salemi, Domenico ;

Agueli, Cecilia ;

La Rosa, Maria ;

Dagnino, Lea ;

Civiletto, Gabriele ;

Messana, Francesca ;

Marfia, Anna ;

Bica, Maria Grazia ;

Cascio, Lucia ;

Floridia, Pietro Michele ;

Mineo, Angelo M. ;

Russo, Mario ;

Fabbiano, Francesco ;

Santoro, Alessandra .

AMERICAN JOURNAL OF HEMATOLOGY, 2010, 85 (05) :331-339

[6] T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer [J].

Cobb, BS ;

Nesterova, TB ;

Thompson, E ;

Hertweck, A ;

O'Connor, E ;

Godwin, J ;

Wilson, CB ;

Brockdorff, N ;

Fisher, AG ;

Smale, ST ;

Merkenschlager, M .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (09) :1367-1373

[7] Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice [J].

Costinean, S ;

Zanesi, N ;

Pekarsky, Y ;

Tili, E ;

Volinia, S ;

Heerema, N ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (18) :7024-7029

[8] A Functional Screen to Identify Novel Effectors of Hematopoietic Stem Cell Activity [J].

Deneault, Eric ;

Cellot, Sonia ;

Faubert, Amelie ;

Laverdure, Jean-Philippe ;

Frechette, Melanie ;

Chagraoui, Jalila ;

Mayotte, Nadine ;

Sauvageau, Martin ;

Ting, Stephen B. ;

Sauvageau, Guy .

CELL, 2009, 137 (02) :369-379

[9] MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation [J].

Fontana, Laura ;

Pelosi, Elvira ;

Greco, Paolo ;

Racanicchi, Serena ;

Testa, Ugo ;

Liuzzi, Francesca ;

Croce, Carlo M. ;

Brunetti, Ercole ;

Grignani, Francesco ;

Peschle, Cesare .

NATURE CELL BIOLOGY, 2007, 9 (07) :775-U90

[10] CD34+hematopoietic stem-progenitor cell microRNA expression and function: A circuit diagram of differentiation control [J].

Georgantas, Robert W., III ;

Hildreth, Richard ;

Morisot, Sebastien ;

Alder, Jonathan ;

Liu, Chang-gong ;

Heimfeld, Shelly ;

Calin, George A. ;

Croce, Carlo M. ;

Civin, Curt I. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (08) :2750-2755

← 1 2 3 4 →