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Stem Cells and Asymmetric Cell Division

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Regenerative Medicine

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Abstract

Asymmetric stem cell division is a fundamental process used to generate cellular diversity and to provide a source of new cells in developing and adult ­organisms. Asymmetric stem cell division leads to another stem cell via ­self-renewal, and a second cell type which can be either a differentiating progenitor or a ­postmitotic cell. Experimental studies in model organisms including the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster and the laboratory mouse, Mus ­musculus, have identified interrelated mechanisms that regulate ­asymmetric stem cell division from polarity formation and mitotic spindle orientation to asymmetric segregation of cell fate determinants and growth control. These mechanisms are mediated by evolutionary conserved molecules including Aurora-A, aPKC, Mud/NuMa, Lgl, Numb and Brat/TRIM-NHL, which in turn regulate a binary switch between stem cell self-renewal and differentiation. The mechanistic insights into asymmetric cell division have enhanced our understanding of stem cell biology and are of major therapeutic interest for regenerative medicine as ­asymmetrically dividing stem cells provide a powerful source for targeted cell replacement and tissue regeneration.

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Abbreviations

Ago1 :

Argonaute protein 1

AurA :

Aurora-A

Baz :

Bazooka

Brat :

Brain tumor

Cdc2 :

Cell division cycle 2

Cdc42 :

Cell division cycle 42

Cdc25 :

Cell division cycle 25

Cdk :

cyclin dependent kinase

Cnn :

centrosomin

CNS :

Central Nervous System

c-Myc :

cellular myelocytomatosis oncogene

DaPKC :

Drosophila atypical protein kinase C

Dctn1 :

dynactin

Dlg :

Discs large

DmPar6 :

Drosophila melanogaster Partitioning defective 6

ESC :

embryonic stem cell

ECT-2 :

epithelial cell transforming gene 2

Galphai :

G-protein alpha, subunit i

GMC :

Ganglion Mother Cell

GoLoco :

G-protein 0, Locomotion defects domain

GDPase :

guanosine diphosphatase

GTPase :

guanosine triphosphatase

Insc :

Inscuteable

Khc-73 :

Kinesin heavy chain 73

Lgl :

Lethal (2) giant larvae

Mira :

Miranda

Mud :

Mushroom body defect

NB :

Neuroblast

NHL :

NCL-1, HT2A, and LIN-41 domain

NuMa :

Nuclear Mitotic apparatus

PAR :

partitioning defective

Par-3 :

partitioning defective 3

Par-6 :

partitioning defective 6

PDZ :

Post synaptic density 95, Discs large, and Zonula occludens-1 domain

Pins :

Partner of Inscuteable

Pon :

Partner of Numb

Pros :

Prospero

RNA :

Ribonucleic Acid

Sqh :

Spaghetti squash

TRIM 3 :

tripartite motif protein 3

TRIM 32 :

tripartite motif protein 32

VNC :

Ventral Nerve Cord

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Acknowledgements

Work in the Hirth laboratory is supported by grants from the UK Medical Research Council (G070149), the Royal Society (Hirth/2007/R2), the Parkinson’s Disease Society (G-0714), the Motor Neurone Disease Association (Hirth/Oct07/6233), and the Fondation Thierry Latran (Hirth/DrosALS).

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  1. Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King’s College London, 37, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK

    Frank Hirth B.Sc., M.Sc., Ph.D., PD

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  1. Frank Hirth B.Sc., M.Sc., Ph.D., PD
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Correspondence to Frank Hirth B.Sc., M.Sc., Ph.D., PD .

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  1. Klinik und Poliklinik für Herzchirurgie, Universitätsklinikum Rostock, Schillingallee 35, Rostock, 18057, Germany

    Gustav Steinhoff

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Hirth, F. (2013). Stem Cells and Asymmetric Cell Division. In: Steinhoff, G. (eds) Regenerative Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5690-8_4

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