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Stem Cells and Asymmetric Cell Division

  • Rita Sousa-NunesEmail author
  • Frank HirthEmail author
Chapter

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 fruitfly Drosophila melanogaster, and the mouse Mus musculus, have identified 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.

Keywords

Stem cell Progenitor cell Neural stem cell Neuroblast Cell polarity Apicobasal polarity Asymmetric cell division Self-renewal Differentiation Cell fate determinant Growth Proliferation Mitotic spindle orientation Centrosome Primary cilium Midbody Drosophila C. elegans Mouse Cell replacement Tissue regeneration Cancer 

List of Abbreviations

Ago1

Argonaute protein 1

AurA

Aurora-A

Baz

Bazooka

Brat

Brain tumor

Cdc42

Cell division cycle 42

C. elegans

Caenorhabditis elegans

Cnn

Centrosomin

CNS

Central Nervous System

c-Myc

cellular Myelocytomatosis oncogene

aPKC

atypical Protein Kinase C

Dlg

Discs large

EpiSC

epiblast stem cells

ES

embryonic stem (cell)

ECT-2

Epithelial cell transforming gene 2

Flfl

Falafel

Gαi

G-protein alpha, subunit i

Gβ13F

G-protein beta at 13 F (cytological location in Drosophila genome)

Gγ1

G-protein gamma 1

GAP

GTPase activating protein

GDI

Guanine dissociation inhibitor

GDP

Guanosine diphosphate

GDPase

Guanosine diphosphatase

GEF

Guanine exchange factor

GMC

ganglion mother cell

GTP

Guanosine-5'-triphosphate

GTPase

Guanosine triphosphatase

Hh

Hedgehog

INP

intermediate neural precursor

Insc

Inscuteable

iPS

induced pluripotent stem (cells)

Jar

Jaguar

Khc-73

Kinesin heavy chain 73

KIF13B

Kinesin Family Member 13B

KLP23

Kinesin-Like Protein 23

Lgl

Lethal (2) giant larvae

LGN

Leucine-Glycine-Asparagine repeats-containing protein (also known as G-protein-signaling modulator 2, GPSM2)

Mira

Miranda

mRNA

messenger Ribonucleic Acid

Mts

Microtubule star

Mud

Mushroom body defect

NHL

NCL-1, HT2A, and LIN-41 (protein domain)

Nin

Ninein

NudE

Nuclear distribution E

NuMA

Nuclear Mitotic Apparatus

PAR

Partitioning defective

Par-3

Partitioning defective 3

Par-6

Partitioning defective 6

Pav

Pavarotti

PCM

pericentriolar material

PCP

planar cell polarity

PDZ

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

Pins

Partner of Inscuteable

Pon

Partner of Numb

PP2A

Protein Phosphatase 2A

Pros

Prospero

Prox1

Prospero homeobox protein 1

RNA

Ribonucleic Acid

SOP

sensory organ precursor (of Drosophila)

Sqh

Spaghetti squash

TRIM 3

Tripartite motif protein 3

TRIM 32

Tripartite motif protein 32

Zip

Zipper

Notes

Acknowledgements

Given the vast amount of literature on the topic, we favoured citation of a variety of review articles when referring to general concepts, and reserved primary citations for when that was not possible or when referring to specific molecular mechanisms. Work in the Sousa-Nunes laboratory is supported by a Cancer Research UK Career Development Fellowship; work in the Hirth laboratory is supported by grants from the UK Medical Research Council (G070149; MR/L010666/1), the Royal Society (Hirth/2007/R2), the Motor Neurone Disease Association (Hirth/Mar12/6085), and Alzheimer’s Research UK (Hirth/ARUK/2012).

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.MRC Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK
  2. 2.Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK

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