Differentiation Of Progenitor Cell Populations Research Articles

The impact of the immune system on lung injury and regeneration in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a devastating respiratory condition that manifests via persistent inflammation, emphysema development and small airway remodeling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the microenvironment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarize recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes; the mechanisms via which myeloid cells cause alveolar degradation, the consequences of inefficient apoptotic cell removal, the formation of tertiary lymphoid structures and the production of autoreactive antibodies and the effects of innate and adaptive immune cell signaling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and human ex vivo lung models can delineate immune cell-epithelium crosstalk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.

Hippo signaling promotes lung epithelial lineage commitment by curbing Fgf10 and β-catenin signaling.

Organ growth and tissue homeostasis rely on the proliferation and differentiation of progenitor cell populations. In the developing lung, localized Fgf10 expression maintains distal Sox9-expressing epithelial progenitors and promotes basal cell differentiation in the cartilaginous airways. Mesenchymal Fgf10 expression is induced by Wnt signaling but inhibited by Shh signaling, and epithelial Fgf10 signaling activates β-catenin signaling. The Hippo pathway is a well-conserved signaling cascade that regulates organ size and stem/progenitor cell behavior. Here, we show that Hippo signaling promotes lineage commitment of lung epithelial progenitors by curbing Fgf10 and β-catenin signaling. Our findings show that both inactivation of the Hippo pathway (nuclear Yap) or ablation of Yap result in increased β-catenin and Fgf10 signaling, suggesting a cytoplasmic role for Yap in epithelial lineage commitment. We further demonstrate redundant and non-redundant functions for the two nuclear effectors of the Hippo pathway, Yap and Taz, during lung development.

Conductive biomaterials for tissue engineering applications

Abstract Conductive biomaterials with a suitable biocompatibility have been utilized to fabricate in vitro platforms for differentiation of progenitor cell population as well as implantable tissue engineering scaffolds. This review evaluates biocompatibility of various conductive biomaterials and relevant fabrication techniques including coating, incorporation into composites, and functionalization with biological moieties. In addition, recent developments in tissue engineering applications using various conductive biomaterials are discussed in detail. Therefore, this overview could provide fundamental knowledge for engineering strategies in regulation of stem cell differentiation, maintenance of phenotypic characteristics, and design of functional implantable scaffolds for better regenerative medicines.

Phenotypic Variations in Chondrocyte Subpopulations and Their Response to In Vitro Culture and External Stimuli

Articular cartilage defects have limited capacity to self-repair, and cost society up to 60 billion dollars annually in both medical treatments and loss of working days. Recent developments in cartilage tissue engineering have resulted in many new products coming to market or entering clinical trials. However, there is a distinct lack of treatments which aim to recreate the complex zonal organization of articular cartilage. Cartilage tissue withstands repetitive strains throughout an individual's lifetime and provides frictionless movement between joints. The structure and composition of its intricately organized extracellular matrix varies with tissue depth to provide optimal resistance to loading, ensure ease of movement, and integrate with the subchondral bone. Each tissue zone is specially designed to resist the load it experiences, and maximize the tissue properties needed for its location. It is unlikely that a homogenous solution to tissue repair will be able to optimally restore the function of such a heterogeneous tissue. For zonal engineering of articular cartilage to become practical, maintenance of phenotypically stable zonal cell populations must be achieved. The chondrocyte phenotype varies considerably by zone, and it is the activity of these cells that help achieve the structural organization of the tissue. This review provides an examination of literature which has studied variations in cellular phenotype between cartilage zones. By doing so, we have identified critical differences between cell populations and highlighted areas of research which show potential in the field. Current research has made the morphological and metabolic variations between these cell populations clear, but an ideal way of maintaining these differences in vitro culture is yet to be established. Combinations of delivered growth factors, mechanical loading, and layered three-dimensional culture systems all show potential for achieving this goal. Furthermore, differentiation of progenitor cell populations into chondrocyte subpopulations may also hold promise for achieving large numbers of zonal chondrocytes. Success of the field lies in establishing methods of retaining phenotypically stable cell populations for in vitro culture.

Differential expression of Id genes in multipotent myeloid progenitor cells: Id-1 is induced by early-and late-acting cytokines while Id-2 is selectively induced by cytokines that drive terminal granulocytic differentiation.

Hematopoietic development is regulated by a complex mixture of cytokine growth factors that guide growth and differentiation of progenitor cell populations at different stages in their development. The genetic programs that drive this process are controlled at the molecular level by the type and number of transcriptional regulators coexpressed in the cell. Both positive- and negative-acting helix-loop-helix transcription factors are expressed during hematopoietic development, with the Id-type transdominant negative regulators controlling the net helix-loop-helix activation potential in the cell at any given time. It has been demonstrated that some of these Id factors are involved in the checkpoint at which undifferentiated progenitor cells make the commitment to terminal maturation. Therefore, we sought to determine whether these Id family factors are selectively induced or extinguished by cytokines that act at different points during hematopoiesis. NFS-60, a myeloid progenitor line that proliferates in response to multiple cytokines, was stimulated by treatment with SCF, IL-3, IL-6, G-CSF, and erythropoietin. Id-1 expression correlated tightly with cellular proliferation: it declined when growth factor stimulation was withdrawn and was quickly induced whenever the cell began to proliferate. The regulation of Id-2 was more complex: its expression was slightly upregulated in factor-deprived cells but only strongly reinduced after extended exposure to cytokines that drive granulocytic differentiation (IL-6, G-CSF, and TGFbeta). These data support a cell-cycle regulatory role for Id-1 in multipotent myeloid progenitor cells and a role for Id-2 during terminal granulocytic differentiation.