Stem Cells and Asymmetric Cell Division

Abstract

Asymmetric stem cell division is a widespread process used to generate cellular diversity in developing and adult organisms whilst retaining a steady stem cell pool. When dividing asymmetrically, stem cells self-renew and generate a second cell type, which can be either a differentiating progenitor or a postmitotic cell. Studies in model organisms, most notably the nematode worm Caenorhabditis elegans , the fruitfl y Drosophila melanogaster , and the mouse Mus musculus , have identifi ed interrelated mechanisms that regulate asymmetric cell division, from polarity formation and mitotic spindle orientation, to asymmetric segregation of fate determinants and organelles, that impact growth and proliferation. Mechanisms linking extrinsic signals to cellular asymmetry are also beginning to emerge. These cellular processes are mediated by evolutionary conserved molecules, and together equilibrate numbers of progenitor and differentiated cells. Insights into asymmetric division have enhanced our understanding of stem cell biology and of hypo-or hyper-proliferation as a consequence of its disruption, including cancer formation. These insights are of major interest for regenerative medicine, since asymmetrically dividing stem cells provide a powerful source for targeted cell replacement and tissue regeneration.

In vivo expansion of functionally integrated GABA ergic interneurons by targeted increase in neural progenitors

“…As exemplified here, manipulation of neuronal differentiation and asymmetric NSC division components is worth investigating with the purpose of expanding progenitors and neurons, and whether lost lineages could be replaced like by like. Indeed, pioneering work on Drosophila NSCs led to the identification of conserved molecules and mechanisms also implicated in asymmetric divisions of mammalian NSCs (reviewed in Sousa‐Nunes & Hirth, ). Given the high degree of evolutionary conservation among the mechanisms that control progenitor cell proliferation and lineage specification in insects and mammals (Sousa‐Nunes & Hirth, ), we hypothesize that the concept presented here is likely general and valid in vertebrates.…”

“…Here, we report for the first time in vivo neural progenitor expansion and neural circuit multiplication with lineage resolution analyses. We performed stepwise manipulations of the levels of the homeodomain transcription factor Prospero (Pros), a key player in neuronal specification and a neural tumor suppressor in Drosophila (Sousa‐Nunes & Hirth, ). Pros is expressed in NSCs but asymmetrically segregated into transient progenitors where it drives neuronal differentiation (Li & Vaessin, ; Choksi et al , ).…”

An immobilization technique for long-term time-lapse imaging of explantedDrosophilatissues

“…So-called type I neuroblasts are the most abundant and are found throughout the CNS (Figure 1). They divide asymmetrically to self-renew and generate a transit-amplifying progenitor called ganglion mother cell (GMC) (reviewed by Sousa-Nunes and Hirth, 2016). The GMC then undergoes a terminal division to produce two neuronal and/or glial progeny whereas the self-renewed neuroblast continues to proliferate.…”

“…The L3 CNS is made up of the optic lobe (OL), the central brain (CB) and the ventral nerve cord (VNC) (Sousa-Nunes and Hirth, 2016). Type I neuroblasts (blue), which divide to self-renew and generate a GMC, are most abundant and are present throughout the CNS.…”

Lineage-specific determination of ring neuron circuitry in the central complex ofDrosophila

“…The cytoarchitecture of both the insect and mammalian brain are characterised by neural lineages generated during development by repeated asymmetric divisions of neural stem and progenitor cells (Shen et al, 1998; Kim and Hirth, 2009; Sousa-Nunes and Hirth, 2016). These ontogenetic clones are thought to constitute building blocks of the insect and mammalian brain (Ito and Awasaki, 2008; Rakic, 2009).…”