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      Stem Cells in the Postnatal Pituitary?

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          Abstract

          Tissue-specific stem cells are uncovered in a growing number of organs by their molecular expression profile and their potential for self-renewal, multipotent differentiation and tissue regeneration. Whether the pituitary gland also contains a pool of versatile ’master’ cells that drive homeostatic, plastic and regenerative cell ontogenesis is at present unknown. Here, I will give an overview of data that may lend support to the existence of stem cells in the postnatal pituitary. During the many decades of pituitary research, various approaches have been used to hunt for the pituitary stem cells. Transplantation and regeneration studies advanced chromophobes as possible source of new hormonal cells. Clonogenicity approaches identified pituitary cells that clonally expand to floating spheres, or to colonies in adherent cell cultures. Behavioural characteristics and changes of marginal, follicular and folliculostellate cells during defined developmental and (patho-)physiological conditions have been interpreted as indicative of a stem cell role. Expression of potential stem cell markers like nestin, as well as topographical localization in the marginal zone around the cleft has also been considered to designate pituitary stem cells. Finally, a ‘side population’ was recently identified in the postnatal pituitary which in many other tissues represents a stem cell-enriched fraction. Taken together, in the course of the long-standing study of the pituitary, several arguments have been presented to support the existence of stem cells, and multiple cell types have been placed in the spotlight as possible candidates. However, none of these cells has until now unequivocally been shown to meet all quintessential characteristics of stem cells.

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          Most cited references118

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          CNS stem cells express a new class of intermediate filament protein.

          Multipotential CNS stem cells receive and implement instructions governing differentiation to diverse neuronal and glial fates. Exploration of the mechanisms generating the many cell types of the brain depends crucially on markers identifying the stem cell state. We describe a gene whose expression distinguishes the stem cells from the more differentiated cells in the neural tube. This gene was named nestin because it is specifically expressed in neuroepithelial stem cells. The predicted amino acid sequence of the nestin gene product shows that nestin defines a distinct sixth class of intermediate filament protein. These observations extend a model in which transitions in intermediate filament gene expression reflect major steps in the pathway of neural differentiation.
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            Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system

            Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.
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              Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation.

              Stem cells persist throughout life by self-renewing in numerous tissues including the central and peripheral nervous systems. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects. Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16Ink4a expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2007
                May 2007
                23 February 2007
                : 85
                : 2
                : 110-130
                Affiliations
                Laboratory of Cell Pharmacology, Department of Molecular Cell Biology, University of Leuven, Leuven, Belgium
                Article
                100278 Neuroendocrinology 2007;85:110–130
                10.1159/000100278
                17337880
                24e0a8ff-d650-4b91-9f8d-63c0520715e0
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                References: 192, Pages: 21
                Categories
                Focus on Pituitary Function

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Chromophobes,Stem cell growth factors,Colony-forming units,Sphere formation,Regeneration,Folliculostellate cells,Pituitary,Notch,Stem cells,Side population

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