Gradual Rarefaction of Hematopoietic Precursors and Atrophy in a Depleted microRNA 29a, b and c Environment

Abstract

BackgroundThe 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 SignificanceHere, 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.

Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling

“…1 ), we asked whether inhibition or reduction of this miRNA was beneficial in cardiac disease models in vivo. We did not obtain mice with complete genetic loss of both miR-29 clusters ( miR-29, a/b1, and b2/c ), which is in good agreement with a recent report 27 , according to which the offspring ratio was 1%, with those born dying within few weeks. Therefore, we used mouse lines with partial deficiency of miR-29 variants, that is, mice with miR-29 ab1 −/− b2c +/− or ab1 +/+ b2c −/− genotype.…”

“…Therefore, we used mouse lines with partial deficiency of miR-29 variants, that is, mice with miR-29 ab1 −/− b2c +/− or ab1 +/+ b2c −/− genotype. Again consistent with other studies 27 – 29 , mice with triple-allelic deletion of miR-29 show some growth retardation (Supplementary Fig. 2a ) and increased mortality, whereas mice with miR-29 ab1 +/+ b2c −/− genotype had normal life spans and did neither show any phenotypical effects as, for instance, in body weight nor was there evidence for the induction of fibrosis in other organs (Supplementary Fig.…”

Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation

“…The C1orf132 has recently been shown to encode a long no-coding RNA (lncRNA) which at its 3′ end includes microRNA MIR29B2C [ 7 ]. Whereas the C1orf132 function remains unclear, it is intriguing that in mice, the miR29 family (miR29ab1 and miR29b2c) has been implicated in the self-renewing ability of HSCs as well as determination of organ and body size [ 8 ]. Our results suggest that the C1orf132/MIR29B2C locus could also be important for graft function after HSCT and thus should be studied further as a potential graft function/prognostic marker.…”

The Role of Microrna-29 in Osteoarthritis

“…MiR-29 knockout mice were born healthy and demonstrated no obvious differences compared to littermate controls. Although some studies have found no difference in the birth rate of miR-29 knockout mice (Cushing et al, 2015;Dooley et al, 2016;Swahari et al, 2021) others have reported global knockout birth rates as low as 1% and birth rates for miR-29ab1 deficient mice of 10% (Kauffman et al, 2015;Sassi et al, 2017). Cartilage-specific knockout of miR-29 resulted in a significant reduction in birth rate for AB1-KO and DKO compared to littermate controls (44% and 39% respectively) whereas B2C-KO mice were born at increased rate.…”

“…Knockout of only the miR-29ab1 locus results in a similar, albeit less severe phenotype, characterised again by smaller size, reduced weight, kyphosis, ataxia and premature death by 28-30 weeks of age (Papadopoulou et al, 2015;Dooley et al, 2016;Caravia et al, 2018). In contrast, mice lacking only the miR-29b2c cluster are generally healthy with slight reductions in body weight reported at most (Kauffman et al, 2015;Dooley et al, 2016;Sassi et al, 2017;Caravia et al, 2018).…”