Asrij-ARF1 mediated endocytic control of signaling regulates stemness in drosophila hematopoiesis

Abstract

"Stem cells are unspecialized cells of embryonic, fetal or adult origin, which can give rise to the differentiated and mature cell types in the organism. Their potency to differentiate into different cell types depends on their origin. Embryonic stem cells originate from the inner cell mass of the blastocyst and are pluripotent in nature while adult stem cells are resident, tissue- specific and multipotent with limited differentiation potential (Nichols and Smith, 2011; Snippert and Clevers, 2011). Stem cells, by definition, have the ability to self-renew and perpetuate their own pool. Understanding how stem cell self- renewal is regulated at the cellular level will help in harnessing them for biomedical applications in regenerative therapies. Embryonic and adult stem cells have potential application in treating blood and neurodegenerative disorders, spinal cord injuries and heart diseases (Koerbling and Estrov, 2003; Scadden and Srivastava, 2012). Adult stem cells are essential for tissue re-generation and repair, and hence elucidating mechanisms of their self- renewal and maintenance becomes very important. Self-renewal involves signalling networks that balance proto-oncogenes (promoting self-renewal), gatekeeping tumor suppressors (limiting self-renewal), and care-taking tumor suppressors (maintaining genomic integrity) (Young, 2011). How these signals are finely modulated to maintain homeostasis is an intriguing puzzle. Cell intrinsic signals need to correctly coordinate and integrate with the extrinsic factors such as signals from the extracellular milieu, niche or other environments which maintain the stem cells in the resident tissue (Voog and Jones, 2010). Mutations in the molecules that govern stem cell maintenance lead to the mis-regulation of the signalling circuitry resulting in reduced stem cell function and loss of developmental homeostasis. Cancers may arise from mutations which inappropriately activate or inactivate the stem cell self- renewal program."