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MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets‐1 and Meis1 transcription factors
Author(s) -
Romania Paolo,
Lulli Valentina,
Pelosi Elvira,
Biffoni Mauro,
Peschle Cesare,
Marziali Giovanna
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07382.x
Subject(s) - haematopoiesis , progenitor cell , biology , microbiology and biotechnology , microrna , clonogenic assay , transcription factor , cellular differentiation , progenitor , stem cell , cd34 , cord blood , immunology , cell , genetics , gene
Summary MicroRNAs (miRNAs) control basic biological functions and are emerging as key regulators of haematopoiesis. This study focused on the functional role of MIRN155 on megakaryocytic (MK) differentiation of human cord blood CD34 + haematopoietic progenitor cells (HPCs). MIRN155 , abundantly expressed in early HPCs, decreases sharply during MK differentiation. Functional studies showed that enforced expression of MIRN155 impairs proliferation and differentiation of MK cells. Furthermore, HPCs transfected with MIRN155 showed a significant reduction of their MK clonogenic capacity, suggesting that down‐modulation of this miRNA favours MK progenitor differentiation. Consistent with this observation, MIRN155 down‐regulates, by directly binding to their 3′‐UTR, the expression of Ets‐1 and Meis1, two transcription factors with well‐known functions in MK cells. These results show that the decline of MIRN155 is required for MK proliferation and differentiation at progenitors and precursors level and indicate that sustained expression of MIRN155 inhibits megakaryopoiesis.