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© The Rockefeller University Press, 0021-9525/1997//1395 $5.00
The Journal of Cell Biology, Volume 138, Number 6, , 1997 1395-1407


Article

Thrombomucin, a Novel Cell Surface Protein that Defines Thrombocytes and Multipotent Hematopoietic Progenitors



Kelly M. McNagny*, Inger Pettersson*, Fabio Rossi*, Ingo Flamme§, Andrej Shevchenko{ddagger}, Matthias Mann{ddagger}, and Thomas Graf*

* Cell Regulation Program, and {ddagger} Protein and Peptide Program, European Molecular Biology Laboratory, Heidelberg, D-69117 Germany; and § Max-Planck Institut for Physiology and Clinical Research, W.G. Kerckhoff-Institute, Department of Molecular Cell Biology, Bad Nauheim, D-61231 Germany

MEP21 is an avian antigen specifically expressed on the surface of Myb-Ets–transformed multipotent hematopoietic precursors (MEPs) and of normal thrombocytes. Using nanoelectrospray tandem mass spectrometry, we have sequenced and subsequently cloned the MEP21 cDNA and named the gene thrombomucin as it encodes a 571–amino acid protein with an extracellular domain typical of the mucin family of proteoglycans. Thrombomucin is distantly related to CD34, the best characterized and most used human hematopoietic stem cell marker. It is also highly homologous in its transmembrane/intracellular domain to podocalyxinlike protein–1, a rabbit cell surface glycoprotein of kidney podocytes.

Single cell analysis of yolk sac cells from 3-d-old chick embryos revealed that thrombomucin is expressed on the surface of both lineage-restricted and multipotent progenitors. In the bone marrow, thrombomucin is also expressed on mono- and multipotent progenitors, showing an overlapping but distinct expression pattern from that of the receptor-type stem cell marker c-kit. These observations strengthen the notion that the Myb-Ets oncoprotein can induce the proliferation of thrombomucin-positive hematopoietic progenitors that have retained the capacity to differentiate along multiple lineages. They also suggest that thrombomucin and CD34 form a family of stem cell–specific proteins with possibly overlapping functions in early hematopoietic progenitors.


Abbreviations used in this paper: cMGF, chicken myelomonocytic growth factor; MEP, Myb-Ets-transformed progenitors; PCLP, podocalyxinlike protein; SCF, stem cell factor.

Please address all correspondence to Thomas Graf, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany. Tel.: 49-62-21-387-411. Fax: 49-62-21-387-516. e-mail: Graf{at}EMBL-Heidelberg.de

Work in M. Mann's laboratory is partially supported by a grant from the German Technology Ministry (BMFT). K.M. McNagny was supported by NRSA Fellowship No. F32 HL0736 from the National Heart, Lung, and Blood Institute, National Institutes of Health, and a grant from the Deutsche Forschungsgemeinschaft (SFB229) to T. Graf.



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