Hematopoietic Stem and Progenitor Cells (HSPCs) and Hematopoietic Microenvironment: Molecular and Bioinformatic Studies of the Zebrafish Models

Abstract

Hematopoietic stem cells (HSCs) reside in a specialized microenvironment in a peculiar anatomic location which regulates the maintenance of stem cells and controls its functions. Recent scientific progress in experimental technologies have enabled the specific detection of epigenetic factors responsible for the maintenance and quiescence of the hematopoietic niche, which has improved our knowledge of regulatory mechanisms. The aberrant role of RNA-binding proteins and their impact on the disruption of stem cell biology have been reported by a number of recent studies. Despite recent modernization in hematopoietic microenvironment research avenues, our comprehension of the signaling mechanisms and interactive pathways responsible for integration of the hematopoietic niche is still limited. In the past few decades, zebrafish usage with regards to exploratory studies of the hematopoietic niche has expanded our knowledge for deeper understanding of novel cellular interactions. This review provides an update on the functional roles of different genetic and epigenetic factors and molecular signaling events at different sections of the hematopoietic microenvironment. The explorations of different molecular approaches and interventions of latest web-based tools being used are also outlined. This will help us to get more mechanistic insights and develop therapeutic options for the malignancies.

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

“…Primitive macrophages are produced as part of the so-called ‘primitive’ wave of hematopoiesis, some of which populate the brain to form the microglial population, with a transient ‘intermediate’ wave of hematopoiesis in the posterior blood island, generating neutrophils [ 13 ]. Multipotent hematopoietic stem cells (HSCs) initiate the ‘definitive’ wave of hematopoiesis and sustain the process throughout the lifespan [ 14 ], with these HSCs initially homing to the caudal hematopoietic tissue (CHT), equivalent to the mammalian fetal liver, to produce multiple cell lineages, with lymphocyte precursors generated migrating to the thymus to commence the production of T cells [ 12 , 15 ]. HSCs ultimately populate the kidney marrow, equivalent to the mammalian bone marrow, allowing ongoing production of neutrophils, macrophages and other leukocytes, and later B cells, with full immunity including natural killer (NK) cell populations in place by 4–6 weeks post fertilization [ 12 , 15 , 16 ].…”

Molecular Aspects of Hematological Malignancies and Benign Hematological Disorders

“…Our current understanding of the complex architecture of the hematopoietic stem cell niche and the molecular events that take place in this complicated milieu has been enabled by research conducted on zebrafish models. Faisal et al, provide a comprehensive overview of the interactions between hematopoietic stem cells, hematopoietic progenitor cells and the bone marrow microenvironment in zebrafish, with a peculiar focus on epigenetic factors, cell signaling, the role of RNA-binding proteins, as well as novel technologies employed for the characterization of the hematopoietic stem cell niche, including CRISPR/Cas9-based bioinformatics approaches [ 11 ].…”