Maturation‐associated gene expression profiles along normal human bone marrow monopoiesis

Abstract

Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis. Five distinct maturation-associated stages of monocytic precursors were identified and isolated from (fresh) normal human BM through fluorescence-activated cell sorting, and the gene expression profile (GEP) of each monocytic precursor subset was analysed by DNA-oligonucleotide microarrays. Overall, >6000 genes (18% of the genes investigated) were expressed in ≥1 stage of BM monopoiesis at stable or variable amounts, showing early decrease in cell proliferation with increased levels of expression of genes linked with cell differentiation. The here-defined GEP of normal human BM monopoiesis might contribute to better understand monocytic differentiation and the identification of novel monocytic candidate markers, while also providing a frame of reference for the study of monocytic maturation in both neoplastic and non-neoplastic disease conditions involving monocytic precursor cells.

Wharton’s Jelly Mesenchymal Stromal Cells Support the Expansion of Cord Blood–derived CD34+ Cells Mimicking a Hematopoietic Niche in a Direct Cell–cell Contact Culture System

“…Serine carboxypeptidase-1 (SCPEP1) is a secreted serine protease which has been implicated in monopoiesis 44 . Interestingly, in our system, this molecule was expressed only in the DC secretome.…”

“…Since our experiments showed that the CD34 + cells can establish different interactions with WJ-MSCs (i.e., the presence of an adherent and a floating cell fraction within DC), we focused our analysis on extracellular proteins that can recreate in vitro a microenvironment similar to that of a hematopoietic niche. We highlighted the presence of 30 extracellular/exosomal or membrane proteins, listed in Table 3, and we performed a comparative analysis among tested culture conditions to investigate the expression differences 24 –68 . Interestingly, in the DC secretome, we identified a set of 16 exclusively expressed proteins.…”

Whole-Genome DNA Methylation Profiling of CD14+ Monocytes Reveals Disease Status and Activity Differences in Crohn’s Disease Patients

“…Knockdown of SLC17A9 was found to suppress the production of IL6 in THP-1 cells even after LPS stimulation suggesting an amelioration of the pro-inflammatory phenotype [85]. Notably, SLC17A9 has been found to be associated with bone marrow monopoiesis [86]. We also identified DMGs that were functionally involved in alcohol reduction (ZADH2), DNA-binding (ZNF572 and ZNF154), RNA-processing (SLFN13), cytoskeletal reorganization (TRIOBP), brain development (NNAT), and keratinocytes (KRTCAP3), whose relation with CD is not immediately evident.…”

Human monopoiesis is characterized by distinct and stage‐specific gene expression profiles

“…In the current issue of the British Journal of Haematology, de Mello et al () address this gap by presenting a ground‐breaking study focusing on the analysis of gene expression profiles (GEP) in these bone marrow‐derived precursors. Based on the results of the EuroFlow consortium, de Mello et al () were able to characterize a variety of specifically regulated genes and their respective expression pattern changes in five distinct maturation stages and between these stages, respectively. Thus, in addition to cell surface markers, selected pre‐monocytic cell populations can be further assessed by specific GEP.…”

“…The insights provided by this study will enhance our knowledge regarding the regulatory processes and the involved molecules participating in monocytic maturation, especially in the early stages of monopoiesis, whilst also providing a 'frame of reference ' (de Mello et al, 2016) for the assessment of monocyte-derived diseases and disease subtypes. For instance, the comparison of GEP obtained from leukaemic cells with the normal reference GEP will presumably provide promising new targets for both diagnostic approaches and therapeutic intervention.…”