Human multipotent stromal cells from bone marrow and microRNA: Regulation of differentiation and leukemia inhibitory factor expression

被引：192

作者：

Oskowitz, Adam Z. ^{[1
]}

Lu, Jun ^{[5
,6
]}

Penfornis, Patrice ^{[1
]}

Ylostalo, Joni ^{[1
]}

McBride, Jane ^{[4
]}

Flemington, Erik K. ^{[4
]}

Prockop, Darwin J. ^{[1
,3
]}

Pochampally, Radhika ^{[1
,2
]}

机构：

[1] Tulane Univ, Hlth Sci Ctr, Ctr Gene Therapy, New Orleans, LA 70112 USA

[2] Tulane Univ, Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA 70112 USA

[3] Tulane Univ, Hlth Sci Ctr, Dept Biochem, New Orleans, LA 70112 USA

[4] Tulane Univ, Hlth Sci Ctr, Dept Pathol, New Orleans, LA 70112 USA

[5] MIT, Broad Inst, Cambridge, MA 02142 USA

[6] Harvard Univ, Cambridge, MA 02142 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 47期

基金：

美国国家卫生研究院;

关键词：

hsa-mir199a; hsa-mir346; stem cells; plasticity;

D O I：

10.1073/pnas.0809807105

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 [理学]; 0710 [生物学]; 09 [农学];

摘要：

We observed that microRNAs (miRNAs) that regulate differentiation in a variety of simpler systems also regulate differentiation of human multipotent stromal cells (hMSCs) from bone marrow. Differentiation of hMSCs into osteoblasts and adipocytes was inhibited by using lentiviruses expressing shRNAs to decrease expression of Dicer and Drosha, two enzymes that process early transcripts to miRNA. Expression analysis of miRNAs during hMSC differentiation identified 19 miRNAs that were up-regulated during osteogenic differentiation and 20 during adipogenic differentiation, 11 of which were commonly up-regulated in both osteogenic and adipogenic differentiation. In silico models predicted that five of the up-regulated miRNAs targeted leukemia inhibitory factor (LIF) expression. The prediction was confirmed for two of the miRNAs, hsa-mir 199a and hsa-mir346, in that over-expression of the miRNAs decreased LIF secretion by hMSCs. The results demonstrate that differentiation of hMSCs is regulated by miRNAs and that several of these miRNAs target LIF.

引用

页码：18372 / 18377

页数：6

共 37 条

[1]

A facile lentiviral vector system for expression of doxycycline-inducible shRNAs: knockdown of the pre-miRNA processing enzyme Drosha [J].

Aagaard, Lars ;

Amarzguioui, Mohammed ;

Sun, Guihua ;

Santos, Luis C. ;

Ehsani, Ali ;

Prydz, Hans ;

Rossi, John J. .

MOLECULAR THERAPY, 2007, 15 (05) :938-945

[2]

Real-time quantification of microRNAs by stem-loop RT-PCR [J].

Chen, CF ;

Ridzon, DA ;

Broomer, AJ ;

Zhou, ZH ;

Lee, DH ;

Nguyen, JT ;

Barbisin, M ;

Xu, NL ;

Mahuvakar, VR ;

Andersen, MR ;

Lao, KQ ;

Livak, KJ ;

Guegler, KJ .

NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9

[3]

MicroRNAs modulate hematopoietic lineage differentiation [J].

Chen, CZ ;

Li, L ;

Lodish, HF ;

Bartel, DP .

SCIENCE, 2004, 303 (5654) :83-86

[4]

The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation [J].

Chen, JF ;

Mandel, EM ;

Thomson, JM ;

Wu, QL ;

Callis, TE ;

Hammond, SM ;

Conlon, FL ;

Wang, DZ .

NATURE GENETICS, 2006, 38 (02) :228-233

[5]

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

[6]

MicroRNA-143 regulates adipocyte differentiation [J].

Esau, C ;

Kang, XL ;

Peralta, E ;

Hanson, E ;

Marcusson, EG ;

Ravichandran, LV ;

Sun, YQ ;

Koo, S ;

Perera, RJ ;

Jain, R ;

Dean, NM ;

Freier, SM ;

Bennett, CF ;

Lollo, B ;

Griffey, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (50) :52361-52365

[7]

LEUKEMIA INHIBITORY FACTOR IS NECESSARY FOR MAINTENANCE OF HEMATOPOIETIC STEM-CELLS AND THYMOCYTE STIMULATION [J].

ESCARY, JL ;

PERREAU, J ;

DUMENIL, D ;

EZINE, S ;

BRULET, P .

NATURE, 1993, 363 (6427) :361-364

[8]

MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation [J].

Felli, N ;

Fontana, L ;

Pelosi, E ;

Botta, R ;

Bonci, D ;

Facchiano, F ;

Liuzzi, F ;

Lulli, V ;

Morsilli, O ;

Santoro, S ;

Valtieri, M ;

Calin, GA ;

Liu, CG ;

Sorrentino, A ;

Croce, CM ;

Peschle, C .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (50) :18081-18086

[9]

MicroRNAs regulate brain morphogenesis in zebrafish [J].

Giraldez, AJ ;

Cinalli, RM ;

Glasner, ME ;

Enright, AJ ;

Thomson, JM ;

Baskerville, S ;

Hammond, SM ;

Bartel, DP ;

Schier, AF .

SCIENCE, 2005, 308 (5723) :833-838

[10]

miRBase: microRNA sequences, targets and gene nomenclature [J].

Griffiths-Jones, Sam ;

Grocock, Russell J. ;

van Dongen, Stijn ;

Bateman, Alex ;

Enright, Anton J. .

NUCLEIC ACIDS RESEARCH, 2006, 34 :D140-D144

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