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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2244.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3424-3430
HEMATOPOIESIS
Human cord blood CD34+Pax-5+ B-cell
progenitors: single-cell analyses of their gene expression
profiles
Eva Sanz,
Melchor Alvarez-Mon,
Carlos Martínez-A, and
Antonio de
la Hera
From the Laboratory of Immunology and Oncology, Consejo
Superior de Investigaciones Científicas (CSIC)-Alcalá
University Research Associated Unit, Madrid; the Immune System Disease
and Oncology Unit, Príncipe de Asturias University Hospital,
Department of Medicine, Alcalá University, Madrid; and the
Department of Immunology and Oncology, Centro Nacional de
Biotecnología, CSIC, Campus de Cantoblanco, Madrid,
Spain.
Circulating CD34+ cells are used in reparative medicine
as a stem cell source, but they contain cells already committed to different lineages. Many think that B-cell progenitors (BCPs) are
confined to bone marrow (BM) niches until they differentiate into B
cells and that they do not circulate in blood. The prevailing convention is that BCP transit a
CD34+CD19 10+
early-B CD34+CD19+CD10+
B-cell progenitor
(pro-B)CD34CD19+CD10+ B-cell
precursor (pre-B) differentiation pathway within BM. However, populations of CD34+CD10+ and
CD34+CD19+ cells circulate in adult peripheral
blood and neonatal umbilical cord blood (CB) that are operationally
taken as BCPs on the basis of their phenotypes, although they have not
been submitted to a systematic characterization of their gene
expression profiles. Here, conventional
CD34+CD19+CD10+ and novel
CD34+CD19+CD10 BCP populations
are characterized in CB by single-cell sorting and multiplex analyses
of gene expression patterns. Circulating BCP are Pax-5+
cells that span the early-B, pro-B, and pre-B developmental stages, defined by the profiles of rearranged V-D-JH, CD79, VpreB,
recombination activating gene (RAG), and terminal
deoxynucleotidyl transferase (TdT) expression. Contrary to the
expectation, circulating
CD34+CD19CD10+ cells are
essentially devoid of Pax-5+ BCP. Interestingly, the novel
CD34+CD19+CD10 BCP appears to be
the normal counterpart of circulating preleukemic BCPs that undergo
chromosomal translocations in utero months or years before their
promotion into infant acute lymphoblastic B-cell leukemia after
secondary postnatal mutations. The results underscore the power of
single-cell analyses to characterize the gene expression profiles in a
minor population of rare cells, which has broad implications in biomedicine.
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