Background The differentiation process proceeding from stem cells towards the different

Background The differentiation process proceeding from stem cells towards the different committed cell types can be considered as a trajectory towards an attractor of a dynamical process. (G) and monocytic (Mo) pathways. These cultures recapitulate physiological hematopoiesis allowing the analysis of almost real unilineage precursors starting from initial differentiation of HPCs until terminal maturation. By analyzing the expression profile of protein coding genes and microRNAs in unilineage CB E MK G and Mo cultures at sequential stages of differentiation and maturation we observed a coordinated fully interconnected and scalable character of cell populace behaviour in both transcriptome and miRNome spaces reminiscent of an attractor-like dynamics. MiRNome and transcriptome space differed for a still not terminally committed behaviour of microRNAs. Conclusions Consistent with their functions the transcriptome system can be considered as the state space of a cell populace while the constantly evolving miRNA space PTK787 2HCl corresponds to the tuning system necessary to reach the attractor. The behaviour of miRNA machinery could be of great relevance not only for the promise of reversing the differentiated state but even for tumor biology. Background The hematopoietic system is usually a privileged observatory for the study of the highly coordinated process leading to differentiated cells. Hematopoietic proliferation and differentiation PTK787 2HCl PTK787 2HCl is usually sustained by a pool of multipotent self-renewing hematopoietic stem cells (HSCs) which give rise to a hierarchy of progenitor populations (HPCs) with more restricted lineage potential ultimately leading to the production of all types of mature blood cells. HSCs/primitive HPCs give rise to a hierarchy of committed HPCs functionally defined as burst-forming models (BFUs) or colony-forming models (CFUs). The earliest HPCs are multipotent and generate mixed colonies (CFU-GEMM: CFU-granulocytic erythroid macrophage megakaryocyte). Multipotent HPCs differentiate and become gradually committed to specific lineages i.e. HPCs of the erythroid series (early and late BFU-E and CFU-E) the megakaryocytic lineage (BFU-MK and CFU-MK) and the granulo-monocytic lineage (CFU-GM CFU-G CFU-M) [1]. HSCs/HPCs differentiation is usually controlled by the combined effects of hematopoietic growth factors (HGFs) chromatin modifiers transcription factors and microRNAs (miRNAs). MiRNAs are a new class of small non coding PTK787 2HCl RNAs (~22 nucleotides) playing a key role in post-transcriptional regulation of gene expression [2 3 This occurs through degradation or translational repression of target mRNAs by binding to their 3′-untranslated regions [4 5 The human genome encodes ~700 miRNAs located in introns exons or intergenic regions [6 7 Several studies have Rabbit Polyclonal to AARSD1. demonstrated that miRNAs have unique developmental-specific expression or signature since each tissue/cell type produces a specific set of miRNAs [8 9 Beside the enumeration of the different actors playing in the differentiation act we have not to forget that this differentiation process can be considered as a trajectory towards an attractor (i.e. a specific cell type) interesting the cell as a whole with a coordinated change in metabolism gene expression shape general responsiveness to environmental stimuli. In this view the attention is usually no more focused on a single ‘common’ cell behavior with a sequential differential gene activation/repression program but on a mutually interacting ensemble of cells in which the entire transcriptome pattern moves from the initial unstable attractor state (progenitor cells) towards another stable end attractor state (mature cells) [10]. By analyzing both protein coding genes (PCGs) and miRNAs expression during hematopoiesis we gave a proof-of-concept of this attractor-like dynamics and were able to characterize the coordinated and scalable character of cell populace behaviour in both mRNAs and miRNAs spaces. These results allow to envisage a sort of biological statistical mechanics along the lines described by Bar-Yam and colleagues [11] in which the traditional “grasp genes” driven PTK787 2HCl approach may be substituted by a global motion of the system as a whole. We will also discuss the complementary role of transcriptome and miRNome and describe the miRNome as a sort of constantly adjusting control device of the cell populace [12]. Results To investigate the cellular and molecular mechanisms underlying haematopoiesis serum-free culture systems were developed for unilineage.