Abstract
Expression of cell surface markers on human hematopoietic cells has provided a method for characterizing subsets of cells with distinct biological functions. This is largely due to the ability to separate highly purified subpopulations of cells for comparative analysis. Relationships between the cell surface phenotype of these subpopulations and their proliferative and differentiative capacity have been instrumental in defining the hierarchical organization of cells comprising the human hematopoietic system. The identification and isolation of human hematopoietic cells expressing AC133, combined with use of in vitro and in vivo assays, has provided novel insights into the hematopoietic progenitor and stem cell compartment in the human. More recent studies have offered evidence that AC133 expression is not limited to primitive blood cells, but also defines unique cell populations in non-hematopoietic tissues. These findings will be reviewed here in the context of human hematopoiesis and the potential role and utility of AC133 expression in the human.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Corbeil D, Roper K, Weigmann A, Huttner WB . AC133 hematopoietic stem cell antigen: human homologue of mouse kidney prominin or distinct member of a novel protein family? Blood 1998 91: 2625–2626
Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW . A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning Blood 1997 90: 5013–5021
Miraglia S, Godfrey W, Buck D . A response to AC133 hematopoietic stem cell antigen: human homologue of mouse kidney prominin or distinct member of a novel protein family? Blood 1998 91: 4390–4391
Maw MA, Corbeil D, Koch J, Hellwig A, Wilson-Wheeler JC, Bridges RJ, Kumaramanickavel G, John S, Nancarrow D, Roper K, Weigmann A, Huttner WB, Denton MJ . A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration Hum Mol Genet 2000 9: 27–34
Corbeil D, Roper K, Fargeas CA, Joester A, Huttner WB . Prominin: a story of cholesterol, plasma membrane protrusions and human pathology Traffic 2001 2: 82–91
Corbeil D, Roper K, Hellwig A, Tavian M, Miraglia S, Watt SM, Simmons PJ, Peault B, Buck DW, Huttner WB . The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions J Biol Chem 2000 275: 5512–5520
Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW . AC133 a novel marker for human hematopoietic stem and progenitor cells Blood 1997 90: 5002–5012
Gallacher L, Murdoch B, Wu DM, Karanu FN, Keeney M, Bhatia M . Isolation and characterization of human CD34(−)Lin(−) and CD34(+)Lin(−) hematopoietic stem cells using cell surface markers AC133 and CD7 Blood 2000 95: 2813–2820
Watt SM, Butler LH, Tavian M, Buhring HJ, Rappold I, Simmons PJ, Zannettino AC, Buck D, Fuchs A, Doyonnas R, Chan JY, Levesque JP, Peault B, Roxanis I . Functionally defined CD164 epitopes are expressed on CD34(+) cells throughout ontogeny but display distinct distribution patterns in adult hematopoietic and nonhematopoietic tissues Blood 2000 95: 3113–3124
Poznansky MC, Evans RH, Foxall RB, Olszak IT, Piascik AH, Hartman KE, Brander C, Meyer TH, Pykett MJ, Chabner KT, Kalams SA, Rosenzweig M, Scadden DT . Efficient generation of human T cells from a tissue-engineered thymic organoid Nat Biotechnol 2000 18: 729–734
Pasino M, Lanza T, Marotta F, Scarso L, De Biasio P, Amato S, Corcione A, Pistoia V, Mori PG . Flow cytometric and functional characterization of AC133+ cells from human umbilical cord blood Br J Haematol 2000 108: 793–800
Matsumoto K, Yasui K, Yamashita N, Horie Y, Yamada T, Tani Y, Shibata H, Nakano T . In vitro proliferation potential of AC133 positive cells in peripheral blood Stem Cells 2000 18: 196–203
Goussetis E, Theodosaki M, Paterakis G, Peristeri J, Petropoulos D, Kitra V, Papassarandis C, Graphakos S . A functional hierarchy among the CD34+ hematopoietic cells based on in vitro proliferative and differentiative potential of AC133+CD34bright and AC133dim/-CD34+ human cord blood cells J Hematother Stem Cell Res 2000 9: 827–840
Majka M, Ratajczak J, Machalinski B, Carter A, Pizzini D, Wasik MA, Gewirtz AM, Ratajczak MZ . Expression, regulation and function of AC133, a putative cell surface marker of primitive human haematopoietic cells Folia Histochem Cytobiol 2000 38: 53–63
Watt SM, Buhring HJ, Rappold I, Chan JY, Lee-Prudhoe J, Jones T, Zannettino AC, Simmons PJ, Doyonnas R, Sheer D, Butler LH . CD164, a novel sialomucin on CD34(+) and erythroid subsets, is located on human chromosome 6q21 Blood 1998 92: 849–866
Wuchter C . Impact of CD133 (AC133) and CD90 expression analysis for acute leukemia immunophenotyping Haematologica 2001 86: 154–161
Rappold I, Watt SM, Kusadasi N, Rose-John S, Hatzfeld J, Ploemacher RE . Gp130-signaling synergizes with FL and TPO for the long-term expansion of cord blood progenitors Leukemia 1999 13: 2036–2048
Filip S, Vavrova J, Vokurkova D, Blaha M, Vanasek J . Myeloid differentiation and maturation of SCF+IL-3+IL-11 expanded AC133+/CD34+ cells selected from high-risk breast cancer patients Neoplasma 2000 47: 73–80
Clark RE . Antisense therapeutics in chronic myeloid leukaemia: the promise, the progress and the problems Leukemia 2000 14: 347–355
Hammert LC, Ball ED . Purging marrow or peripheral blood stem cells for autografting Curr Opin Hematol 1997 4: 423–428
Margolis J, Borrello I, Flinn IW . New approaches to treating malignances with stem cell transplantation Semin Oncol 2000 27: 524–530
Bruserud O, Tjonnfjord G, Gjertsen BT, Foss B, Ernst P . New strategies in the treatment of acute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients Stem Cells 2000 18: 343–351
Bonnet D, Dick JE . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell Nat Med 1997 3: 730–737
Petzer AL, Eaves CJ, Lansdorp PM, Ponchio L, Barnett MJ, Eaves AC, Bruserud O, Tjonnfjord G, Gjertsen BT, Foss B, Ernst P . Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia Blood 1996 88: 2162–2171
Fauth F, Weidmann E, Martin H, Schneider B, Sonnhoff S, Hoelzer D . AC133 expression on acute myeloid leukemia blasts: correlation to FAB and to CD34 expression and possible implications for peripheral blood progenitor cell purging in AML Leukemia Res 2001 25: 191–196
Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D . Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells Blood 1999 93: 1435–1437
Kratz-Albers K, Zuhlsdorp M, Leo R, Berdel WL, Buchner T, Serve H . Expression of a AC133, a novel stem cell marker, on human leukemic blasts lacking CD34-antigen and on a human CD34+ leukemic line:MUTZ-2 Blood 1998 92: 4485–4487
Waller CF, Martens UM, Lange W . Philadelphia chromosome-positive cells are equally distributed in AC133+ and AC133− fractions of CD34+ peripheral blood progenitor cells from patients with CML Leukemia 1999 13: 1466–1467
Baersch G, Baumann M, Ritter J, Jurgens H, Vormoor J . Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia Br J Haematol 1999 107: 572–580
Buhring HJ, Seiffert M, Marxer A, Weiss B, Faul C, Kanz L, Brugger W . AC133 antigen expression is not restricted to acute myeloid leukemia blasts but is also found on acute lymphoid leukemia blasts and on a subset of CD34+ B-cell precursors Blood 1999 94: 832–833
Ebener U, Brinkmann A, Zotova V, Niegemann E, Wehner S . Expression of AC133 vs. CD34 in acute childhood leukemias Klin Padiatr 2000 212: 90–98
Dick JE . Normal and leukemic human stem cells assayed in SCID mice Semin Immunol 1996 8: 197–206
Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S . Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors Blood 2000 95: 952–958
Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S . Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells Circ Res 2001 88: 167–174
Buhring HJ, Seiffert M, Bock TA, Scheding S, Thiel A, Scheffold A, Kanz L, Brugger W . Expression of novel surface antigens on early hematopoietic cells Ann NY Acad Sci 1999 872: 25–38; discussion 38–29
Bhatia M, Bonnet D, Murdoch B, Gan OI, Dick JE . A newly discovered class of human hematopoietic cells with SCID-repopulating activity Nat Med 1998 4: 1038–1045
Storms RW, Goodell MA, Fisher A, Mulligan RC, Smith C, Bruserud O, Tjonnfjord G, Gjertsen BT, Foss B, Ernst P . Hoechst dye efflux reveals a novel CD7(+)CD34(−) lymphoid progenitor in human umbilical cord blood Blood 2000 96: 2125–2133
Hess DA, Gallacher L, Wu D, Murdoch B, Keeney M, Chin-Yee I, Howsen-Jan K, Ottowski P, Foley R, White M, Bhatia M . Direct comparison of the repopulating capacity of human stem cells mobilized with G-CSF versus G-CSF in combination with SCF in the NOD/SCID mouse (submitted)
Murdoch B, Gallacher L, Chadwick K, Jay K, Wu D, Hawley RG, Bhatia M . Retroviral gene transfer into CD34−AC133+ cells (submitted)
Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL . Direct isolation of human central nervous system stem cells Proc Natl Acad Sci USA 2000 97: 14720–14725
Shamblott MJ, Axelman J, Littlefield JW, Blumenthal PD, Huggins GR, Cui Y, Cheng L, Gearhart JD . Human embryonic germ cell derivatives express a broad range of developmentally distinct markers and proliferate extensively in vitro Proc Natl Acad Sci USA 2001 98: 113–118
Acknowledgements
This work was supported by a grant from the Cancer Research Society of Canada, and a scholarship award (No. MSH-35681) to MB from the Canadian Institutes of Health Research, Ontario, Canada.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bhatia, M. AC133 expression in human stem cells. Leukemia 15, 1685–1688 (2001). https://doi.org/10.1038/sj.leu.2402255
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2402255
Keywords
This article is cited by
-
Transplantation of mesenchymal stem cells into the renal medulla attenuated salt-sensitive hypertension in Dahl S rat
Journal of Molecular Medicine (2014)
-
COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients After Acute Myocardial Infarction and Left Ventricular Dysfunction: Study Rationale and Design
Journal of Cardiovascular Translational Research (2010)
-
Haematopoietic repopulating activity in human cord blood CD133+ quiescent cells
Bone Marrow Transplantation (2009)
-
Contribution of human hematopoietic stem cells to liver repair
Seminars in Immunopathology (2009)