Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 156K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rebel, V. I. Articles by Sieff, C. A. Search for Related Content PubMed PubMed Citation Articles by Rebel, V. I. Articles by Sieff, C. A. Social Bookmarking                            What's this?

Original Article

^a Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
^b Department of Hematology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
^c Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
Dana-Farber Cancer Institute, Rm. M613, 44 Binney St., Boston, MA 02115.617-632-5757617-632-2070

vivienne_rebel{at}dfci.harvard.edu

Hematopoietic stem cell (HSC) self-renewal is a complicated process, and its regulatory mechanisms are poorly understood. Previous studies have identified tumor necrosis factor (TNF)- as a pleiotropic cytokine, which, among other actions, prevents various hematopoietic progenitor cells from proliferating and differentiating in vitro. However, its role in regulating long-term repopulating HSCs in vivo has not been investigated. In this study, mice deficient for the p55 or the p75 subunit of the TNF receptor were analyzed in a variety of hematopoietic progenitor and stem cell assays. In older p55^–/– mice (>6 mo), we identified significant differences in their hematopoietic system compared with age-matched p75^–/– or wild-type counterparts. Increased marrow cellularity and increased numbers of myeloid and erythroid colony-forming progenitor cells (CFCs), paralleled by elevated peripheral blood cell counts, were found in p55-deficient mice. In contrast to the increased myeloid compartment, pre-B CFCs were deficient in older p55^–/– mice. In addition, a fourfold decrease in the number of HSCs could be demonstrated in a competitive repopulating assay. Secondary transplantations of marrow cells from primary recipients of p55^–/– marrow revealed impaired self-renewal ability of p55-deficient HSCs. These data show that, in vivo, signaling through the p55 subunit of the TNF receptor is essential for regulating hematopoiesis at the stem cell level.

Key Words: hematopoietic stem cell • cell differentiation • cytokine receptors

Abbreviations used in this paper: BFU-E, erythroid burst-forming unit; BM, bone marrow; CFC, colony-forming cell; CFU-GEMM, multilineage CFU; CFU-G/M, granulocyte/macrophage CFU; CFU-S, CFU in the spleen; CRU, competitive repopulating unit(s); HSC, hematopoietic stem cell; Lin, lineage; PB, peripheral blood; PI, propidium iodide; SSC, side scatter; WBC, white blood cell; WT, wild-type.

J.L.M. Ferrara and C.A. Sieff contributed equally to this paper.

© 1999 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS