期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 13, 页码 5925-5930出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907942107
关键词
B1 and B2 cells; CD19, a Pax5 reporter stepwise acquisition; layered B-lymphocyte lineages; single-cell gene and protein expression profiles; umbilical cord blood
资金
- Ministries of Health [FIS04/1889, FIS/CIBEREHD]
- Research and Innovation [GEN-2001-4856-C13-13, SAF2004-8138]
- Madrid State [MITIC-CM-BIO-0189/2006]
Studies here respond to two long-standing questions: Are human pre/pro-B CD34(+)CD10(-)CD19(+) and common lymphoid progenitor (CLP)/early-B CD34(+)CD10(+)CD19(-) alternate precursors to pro-B CD34(+)CD19(+)CD10(+) cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig V-H-D-J(H) sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34(high)Lineage(-) pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34(+)CD45RA(+)CD10(-)CD19(-)) directly generate an initial wave of Pax5(+)TdT(-) unilineage pre/pro-B cells and a later wave of multilineage CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the V-H-D-J(H) Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5(+)TdT(-) pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway.
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