Open AccessGradual Rarefaction of Hematopoietic Precursors and Atrophy in a Depleted microRNA 29a, b and c Environment
Author(s) -
Lauren Rachel Kauffman,
Veronica Balatti,
Luciano Cascione,
Paolo Fadda,
Frederick Racke,
Ramasamy Santhanam,
Stefan Costinean
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0131981
Subject(s) - bone marrow , haematopoiesis , biology , phenotype , knockout mouse , hematopoietic stem cell , microbiology and biotechnology , stem cell , immunology , genetics , gene
Background The self-renewing ability of HSCs is fundamental for the maintenance of a pool of bone marrow precursors throughout the life of an individual. The genetic mechanisms underlying such a complex process are still poorly understood. Results and Significance Here, we show that constitutive in vivo deletion of miR29ab1 leads to reduced number of HSCs and that miR29ab1 deficient bone marrow cannot repopulate the bone marrow of irradiated mice. An Affymetrix analysis of the miR29ab1 knockout mice identifies key proteins that could be responsible for this phenotype, as DNMT3a and b. Moreover, our findings reveal that whereas miR29b2c knockout mice do not exhibit any spontaneous abnormality, the double knock out – miR29ab1b2c – has marked generalized atrophy, raising the possibility that the two bi-cistrons might cooperate in order to maintain the stem cell number in general, not only limited to the bone marrow.