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Stem Cells and Asymmetric Cell Division

  • Frank Hirth
Chapter

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.

Keywords

Stem Cell Mitotic Spindle Polarity Formation Asymmetric Cell Division Asymmetric Localisation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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

Notes

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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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of PsychiatryKing’s College LondonLondonUK

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