Single-cell analysis of early B-lymphocyte development suggests independent regulation of lineage specification and commitment in vivo
2012 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 39, 15871-15876 p.Article in journal (Refereed) Published
To better understand the process of B-lymphocyte lineage restriction, we have investigated molecular and functional properties in early B-lineage cells from Pax-5-deficient animals crossed to a B-lineage-restricted reporter mouse, allowing us to identify B-lineage-specified progenitors independently of conventional surface markers. Pax-5 deficiency resulted in a dramatic increase in the frequency of specified progenitor B-cellsmarked by expression of a lambda 5 (Igll1) promoter-controlled reporter gene. Gene expression analysis of ex vivo isolated progenitor cells revealed that Pax-5 deficiency has a minor impact on B-cell specification. However, single-cell in vitro differentiation analysis of ex vivo isolated cells revealed that specified B-lineage progenitors still displayed a high degree of plasticity for development into NK or T lineage cells. In contrast, we were unable to detect any major changes in myeloid lineage potential in specified Pax-5-deficient cells. By comparison of gene expression patterns in ex vivo isolated Pax-5-and Ebf-1-deficient progenitors, it was possible to identify a set of B-cell-restricted genes dependent on Ebf-1 but not Pax-5, supporting the idea that B-cell specification and commitment is controlled by distinct regulatory networks.
Place, publisher, year, edition, pages
National Academy of Sciences , 2012. Vol. 109, no 39, 15871-15876 p.
transcription, Notch-1, Deltex
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-85090DOI: 10.1073/pnas.1210144109ISI: 000309604500070OAI: oai:DiVA.org:liu-85090DiVA: diva2:564620
Funding Agencies|Swedish Cancer Society||Swedish Research Council||Swedish Childhood Cancer Foundation||faculty of Medicine at Linkoping University||2012-11-022012-11-022015-02-16