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Dicer is selectively important for the earliest stages of erythroid development.

TitleDicer is selectively important for the earliest stages of erythroid development.
Publication TypeJournal Article
Year of Publication2012
AuthorsBuza-Vidas N, Cismasiu VB, Moore S, Mead AJ, Woll PS, Lutteropp M, Melchiori L, Luc S, Bouriez-Jones T, Atkinson D, O'Carroll D, Jacobsen SEirik W, Nerlov C
Date Published2012 Sep 20
KeywordsAnimals, Biological Markers, Blotting, Western, Cell Differentiation, Cell Lineage, DEAD-box RNA Helicases, Erythroid Cells, Gene Expression Profiling, Gene Expression Regulation, Hematopoietic Stem Cells, Integrases, Megakaryocyte Progenitor Cells, Mice, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA, Messenger, Transcription Factors

MicroRNAs (miRs) are involved in many aspects of normal and malignant hematopoiesis, including hematopoietic stem cell (HSC) self-renewal, proliferation, and terminal differentiation. However, a role for miRs in the generation of the earliest stages of lineage committed progenitors from HSCs has not been identified. Using Dicer inactivation, we show that the miR complex is not only essential for HSC maintenance but is specifically required for their erythroid programming and subsequent generation of committed erythroid progenitors. In bipotent pre-MegEs, loss of Dicer up-regulated transcription factors preferentially expressed in megakaryocyte progenitors (Gata2 and Zfpm1) and decreased expression of the erythroid-specific Klf1 transcription factor. These results show a specific requirement for Dicer in acquisition of erythroid lineage programming and potential in HSCs and their subsequent erythroid lineage differentiation, and in particular indicate a role for the miR complex in achieving proper balance of lineage-specific transcriptional regulators necessary for HSC multilineage potential to be maintained.

Alternate JournalBlood
PubMed ID22869792
Grant ListG0501838 / / Medical Research Council / United Kingdom
G0701761 / / Medical Research Council / United Kingdom
G0801073 / / Medical Research Council / United Kingdom
G0900892 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
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