ABSTRACT
Sickle cell disease (SCD) is one of the most common haemoglobinopathies worldwide, with up to 70 % of global SCD annual births occurring in sub-Saharan Africa. Reports have shown that 50 to 80 % of affected children in these countries die annually. Efforts geared towards understanding and controlling HbF production in SCD patients could lead to strategies for effective control of globin gene expression and therapeutic approaches that could be beneficial to individuals with haemoglobinopathies. Hemopoietic stem cells (HSCs) are characterized by a specific miRNA signature in every state of differentiation. The role of miRNAs has become evident both in the maintenance of the "stemness" and in the early induction of differentiation by modulation of the expression of the master pluripotency genes and during early organogenesis. miRNAs are extra regulatory mechanisms in hematopoietic stem cells (HSCs) via influencing transcription profiles together with transcript stability. miRNAs have been reported to be used to reprogram primary somatic cells toward pluripotency. Their involvement in cell editing holds the potential for therapy for many genetic diseases. This review provides a snapshot of miRNA involvement in cell fate decisions, haemoglobin induction pathway, and their journey as some emerge prime targets for therapy in beta haemoglobinopathies.
Subject(s)
Anemia, Sickle Cell , Hemoglobinopathies , MicroRNAs , Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/genetics , Child , Fetal Hemoglobin/genetics , Fetal Hemoglobin/metabolism , Hematopoietic Stem Cells/metabolism , Hemoglobinopathies/genetics , Hemoglobinopathies/therapy , Humans , MicroRNAs/genetics , MicroRNAs/therapeutic useABSTRACT
Advances in single-cell technology and genetic mouse models have resulted in the identification of new types of hemopoietic stem cells (HSC), resulting in baffling observations, suggesting a reconsideration of the long-held notion that all hematopoietic cells in the adult are derived from HSCs. The existence of long-lived HSC-independent hematopoiesis has led to the conclusion that despite the single hierarchical differentiation route that generates functional blood types, other differentiation routes exist in-vivo. Heterogeneity in the HSC population and the evolving knowledge around HSC has translated to it's improved application as a therapeutic tool for various blood disorders. The reprogramming of non-hematopoietic somatic and mature blood cells to pluripotency with their subsequent differentiation into hematopoietic stem cells/progenitor cells and the introduction of new generation sequencing holds the potential for the resolution of ambiguities involved in HSC bone marrow transplantation. There is a change in the paradigm for HSC transplantation donor selection. Donor choice favors haploidentical HCT than cord blood. This review provides a general overview of the current events around hemopoietic stem cells, with emphasis on the rising trend of HSC transplantation, especially haploidentical stem cell transplantation.
