Essential Role for the p55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level

doi:10.1084/jem.190.10.1493

This Article

	Full Text
	Full Text (PDF, 156K)
	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 HighWire
	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?

© The Rockefeller University Press, 0022-1007/1999/11/1493/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 10, November 15, 1999 1493-1504

Original Article

Essential Role for the p55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level

Vivienne I. Rebel^a,b, Sheila Hartnett^a,b, Geoffrey R. Hill^a,b, Suzan B. Lazo-Kallanian^c, James L.M. Ferrara^a,b, and Colin A. Sieff^a,b
^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

Correspondence to: Vivienne I. Rebel, Dana-Farber Cancer Institute, Rm. M613, 44 Binney St., Boston, MA 02115. Tel:617-632-2070 Fax:617-632-5757 E-mail:vivienne_rebel{at}dfci.harvard.edu.

Hematopoietic stem cell (HSC) self-renewal is a complicatedprocess, and its regulatory mechanisms are poorly understood.Previous studies have identified tumor necrosis factor (TNF)- ${alpha}$ as a pleiotropic cytokine, which, among other actions, preventsvarious hematopoietic progenitor cells from proliferating anddifferentiating in vitro. However, its role in regulating long-termrepopulating HSCs in vivo has not been investigated. In thisstudy, mice deficient for the p55 or the p75 subunit of theTNF receptor were analyzed in a variety of hematopoietic progenitorand stem cell assays. In older p55^-/- mice (>6 mo), we identifiedsignificant differences in their hematopoietic system comparedwith age-matched p75^-/- or wild-type counterparts. Increasedmarrow cellularity and increased numbers of myeloid and erythroidcolony-forming progenitor cells (CFCs), paralleled by elevatedperipheral blood cell counts, were found in p55-deficient mice.In contrast to the increased myeloid compartment, pre-B CFCswere deficient in older p55^-/- mice. In addition, a fourfolddecrease in the number of HSCs could be demonstrated in a competitiverepopulating assay. Secondary transplantations of marrow cellsfrom primary recipients of p55^-/- marrow revealed impaired self-renewalability of p55-deficient HSCs. These data show that, in vivo,signaling through the p55 subunit of the TNF receptor is essentialfor regulating hematopoiesis at the stem cell level.

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

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Xanthoulea, S., Gijbels, M. J.J., van der Made, I., Mujcic, H., Thelen, M., Vergouwe, M. N., Ambagts, M. H.C., Hofker, M. H., de Winther, M. P.J. (2008). p55 Tumour necrosis factor receptor in bone marrow-derived cells promotes atherosclerosis development in low-density lipoprotein receptor knock-out mice. Cardiovasc Res 80: 309-318 [Abstract] [Full Text]
Claessens, Y.-E., Fontenay, M., Pene, F., Chiche, J.-D., Guesnu, M., Hababou, C., Casadevall, N., Dhainaut, J.-F., Mira, J.-P., Cariou, A. (2006). Erythropoiesis Abnormalities Contribute to Early-Onset Anemia in Patients with Septic Shock. Am. J. Respir. Crit. Care Med. 174: 51-57 [Abstract] [Full Text]
Tavener, S. A., Kubes, P. (2006). Cellular and molecular mechanisms underlying LPS-associated myocyte impairment. Am. J. Physiol. Heart Circ. Physiol. 290: H800-H806 [Abstract] [Full Text]
Bijangi-Vishehsaraei, K., Saadatzadeh, M. R., Werne, A., McKenzie, K. A. W., Kapur, R., Ichijo, H., Haneline, L. S. (2005). Enhanced TNF-{alpha}-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signal-regulating kinase 1. Blood 106: 4124-4130 [Abstract] [Full Text]
Shen, W. H., Zhou, J.-H., Broussard, S. R., Johnson, R. W., Dantzer, R., Kelley, K. W. (2004). Tumor Necrosis Factor {alpha} Inhibits Insulin-Like Growth Factor I-Induced Hematopoietic Cell Survival and Proliferation. Endocrinology 145: 3101-3105 [Abstract] [Full Text]
Rebel, V. I., Kung, A. L., Tanner, E. A., Yang, H., Bronson, R. T., Livingston, D. M. (2002). Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal. Proc. Natl. Acad. Sci. USA 99: 14789-14794 [Abstract] [Full Text]
Bryder, D., Ramsfjell, V., Dybedal, I., Theilgaard-Monch, K., Hogerkorp, C.-M., Adolfsson, J., Borge, O. J., Jacobsen, S. E. W. (2001). Self-Renewal of Multipotent Long-Term Repopulating Hematopoietic Stem Cells Is Negatively Regulated by Fas and Tumor Necrosis Factor Receptor Activation. JEM 194: 941-952 [Abstract] [Full Text]
Dybedal, I., Bryder, D., Fossum, A., Rusten, L. S., Jacobsen, S. E. W. (2001). Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells. Blood 98: 1782-1791 [Abstract] [Full Text]
Kung, A. L., Rebel, V. I., Bronson, R. T., Ch'ng, L.-E., Sieff, C. A., Livingston, D. M., Yao, T.-P. (2000). Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev. 14: 272-277 [Abstract] [Full Text]
Hill, G. R., Teshima, T., Rebel, V. I., Krijanovski, O. I., Cooke, K. R., Brinson, Y. S., Ferrara, J. L. M. (2000). The p55 TNF-{alpha} Receptor Plays a Critical Role in T Cell Alloreactivity. J. Immunol. 164: 656-663 [Abstract] [Full Text]