MicroRNAs Modulate Hematopoietic Lineage Differentiation

American Association for the Advancement of Science (AAAS) - Tập 303 Số 5654 - Trang 83-86 - 2004
Chang Zheng Chen1,2, Ling Li1,2, Harvey F. Lodish1,2, David P. Bartel1,2
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
2Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142 USA

Tóm tắt

MicroRNAs (miRNAs) are an abundant class of ∼22-nucleotide regulatory RNAs found in plants and animals. Some miRNAs of plants, Caenorhabditis elegans , and Drosophila play important gene-regulatory roles during development by pairing to target mRNAs to specify posttranscriptional repression of these messages. We identify three miRNAs that are specifically expressed in hematopoietic cells and show that their expression is dynamically regulated during early hematopoiesis and lineage commitment. One of these miRNAs, miR-181, was preferentially expressed in the B-lymphoid cells of mouse bone marrow, and its ectopic expression in hematopoietic stem/progenitor cells led to an increased fraction of B-lineage cells in both tissue-culture differentiation assays and adult mice. Our results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.

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Tài liệu tham khảo

10.1016/S0092-8674(03)00428-8

10.1104/pp.103.023630

10.1038/nature01958

10.1016/0092-8674(93)90529-Y

10.1016/0092-8674(93)90530-4

10.1038/35002607

10.1016/S0092-8674(03)00231-9

10.1016/S0960-9822(03)00250-1

10.1126/science.1080372

10.1038/35040556

10.1016/S0960-9822(03)00287-2

10.1261/rna.2146903

10.1101/gad.1074403

10.1016/S0012-1606(03)00126-X

10.1073/pnas.242606799

10.1073/pnas.86.22.8867

10.1126/science.1064921

10.1016/S0960-9822(02)00809-6

The recent report that miR-23 regulates Hes1 during retinoic acid–induced differentiation ( 28 ) has been called into question because it mistakenly reported the analysis of Homolog of ES1 rather than of Hes1 .

10.1126/science.1065062

J. Dostie, Z. Mourelatos, M. Yang, A. Sharma, G. Dreyfuss, RNA9, 631 (2003).

10.1093/emboj/cdf476

10.1038/nature01957

10.1261/rna.2780503

Materials and methods are available as supporting material on Science Online.

L. S. Collins, K. Dorshkind, J. Immunol.138, 1082 (1987).

10.1016/S0092-8674(00)81215-5

10.1038/nature01730

10.1073/pnas.86.10.3519

We thank N. Lau and B. Reinhart for reagents and advice on the cloning of endogenous Dicer products E. Weinstein for bioinformatic analysis V. Carey for help on statistical analysis and members of the Lodish and Bartel laboratories and P. Zamore for comments on the manuscript. Supported in part by grants from NSF (H.F.L.) and NIH (D.P.B.) and by a Donaldson Lufkin and Jenrette postdoctoral fellowship from the Cancer Research Institute (C.-Z. C.).