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C1qRp defines a new human stem cell population with hematopoietic and hepatic potential

  1. Dominique A. Bonnet†
  1. *Howard Hughes Medical Institute and Abramson Family Cancer Research Institute, ‡Molecular Cardiology Research Center, University of Pennsylvania School of Medicine, BRB-2/3, 421 Curie Boulevard, Philadelphia, PA 19104-6160; †Coriell Institute for Medical Research, Camden, NJ 08043; and§ Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900

  1. Edited by Carlo M. Croce, Thomas Jefferson University, Philadelphia, PA, and approved June 11, 2002 (received for review February 20, 2002)

Abstract

The characterization of two distinct classes of hematopoietic stem cells based on CD34 expression and the ability of human bone marrow (BM) cells to differentiate into nonhematopoietic cells introduced new levels of complexity within the stem cell compartment. Here we report the identification and purification of a rare human stem cell population with hematopoietic and hepatic potential based on the expression of a receptor for the complement molecule C1q (C1qRp). We show that C1qRp is a positive marker of all BM-repopulating stem cells because it is expressed on both CD34− and CD34+ stem cells from umbilical cord blood and adult BM. In addition, we show that highly purified lineage-negative CD45+CD38−CD34+or−C1qRFormula cells not only have BM-repopulating capacity but also can differentiate into human hepatocytes in vivo. The identification of human hepatocytes in mouse livers indicates that the NOD/SCID (nonobese diabetic/severe combined immunodeficient) mouse model can be a valuable tool to study the differentiation potential of adult human stem cells. These findings may have important scientific and clinical implications in the field of human stem cell biology and transplantation.

Footnotes

    • ↵ To whom reprint requests should be addressed at the present address: Cancer Research U.K., London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom. E-mail: dominique.bonnet{at}cancer.org.uk.

    • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviations

    • BM, bone marrow

    • CB, cord blood

    • CFC, colony-forming cells

    • HSA, hepatocyte-specific antigen

    • HSC, hematopoietic stem cell

    • Lin−, lineage-negative

    • LTC-IC, long-term culture-initiating cell

    • NOD/SCID, nonobese diabetic/LtSz-scid

    • SRC, SCID-repopulating cells

    • Received February 20, 2002.

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