For each reference strain the 16S rRNA gene was cloned into a pGEM-T Easy Vector System

, we report an overall compromised mononuclear-phagocyte lineage development in ERK12/2 mice, through PubMed ID: the alteration of M-CSFR expression. Mice defective for M-CSFR mice are severely osteopetrotic, with reduced mononuclear phagocyte production, reduced number of macrophages, and development of a splenomegaly. We found similar characteristics in our model, but with a less severe phenotype. This corroborates the reduced expression of M-CSFR+ cells in ERK12/2 mice. It is well-known that ERK is a downstream effector of M-CSFR and that it contributes to the regulation of myelopoiesis. However, it is to our knowledge, the first demonstration of a control of M-CSFR expression downstream of ERK1. The loss of ERK1 leads to impaired expression of the M-CSFR in myeloid progenitors and induce a delay in their differentiation program, as shown by the accumulation of CMPs in ERK12/2 bone marrow, while the proportion of GMPs was reduced. The fraction of CD115-positive cells on the CMP subset was too low for interpretation. The CMPs have been shown to be divided into three phenotypically, functionally and VS-4718 cost developmentally distinct cell subsets that express or not the M-CSFR. In our study we quantified the MCSFR expression on the overall CMP population. The M-CSFR expression study in the three described subsets in the ERK12/2 ERK1 Regulates the Hematopoietic Stem Cell Niches mice may allow a quantification of the M-CSFR and explain the increase of the CMP compartment. Furthermore, we reported a decrease in the BM monocytic population in ERK12/2 mice. Together, these data suggest that ERK1 plays a key role in myelopoiesis by controlling the expression of M-CSFR. This control does not take place at the transcriptional level, as the expression of the M-CSFR mRNA is not different between WT and ERK12/2, in neither GMP or CMP myeloid progenitors. This means that receptor synthesis is more likely to be governed by posttranscriptional regulation as previously suggested. Thus, we can hypothesize that ERK1 is involved in the posttranscriptional mechanisms regulating the expression of the M-CSFR. In line with this hypothesis, it has been shown that the ERK pathway is involved in the mechanisms that control M-CSFR turnover. In summary, our results show that the microenvironmental default observed in ERK12/2 mice is in fact a consequence of an erroneous myeloid lineage commitment. It has been recently published that the inhibitor of differentiation gene plays a role in regulation of bone and BM physiology. In Id12/2 mice, the osteoporosis phenotype and increased osteoclasts observed are suggested to be due to a decrease of the CMP population. Likewise, our study suggests that GMPs/CMPs are the ERK1 potential cellular targets. The ERK1-regulated M-CSFR expression characterizes one of the mechanisms involved. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. The observed bone and BM microenvironment phenotypes as well as the decreased osteoclastogenesis in ERK12/2 mice are due to an altered homeostasis of the myeloid precursors cells. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments. medium for up to 7 days. Cell proliferation was monitored by means of the fluorimetric metabolic growth indicator Uptiblue at the indicated days. Data show that d

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