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Stem Cells and Asymmetric Cell Division

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Book cover Regenerative Medicine - from Protocol to Patient

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.

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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

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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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Authors and Affiliations

  1. MRC Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, Denmark Hill, 37, London, SE5 8AF, UK

    Rita Sousa-Nunes

  2. Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, New Hunt’s House, Guy’s Campus, London, SE1 1UL, UK

    Frank Hirth

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  1. Rita Sousa-Nunes
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  2. Frank Hirth
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Correspondence to Rita Sousa-Nunes or Frank Hirth .

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Editors and Affiliations

  1. Department of Cardiac Surgery and Refere, University of Rostock, Rostock, Mecklenburg-Vorpomm., Germany

    Gustav Steinhoff

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Sousa-Nunes, R., Hirth, F. (2016). Stem Cells and Asymmetric Cell Division. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-27583-3_3

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