Discovery of a CD10-negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs
We report the presence in fetal tissues of 2 distinct CD19+ B-progenitors, an adult-type CD10+ve ProB-progenitor and a new CD10-ve PreProB-progenitor, and describe their molecular and functional characteristics. PreProB-progenitors and ProB-progenitors appear early in the first trimester in embryonic liver, followed by a sustained second wave of B-progenitor development in fetal bone marrow (BM), where together they form >40% of the total hematopoietic stem cell/progenitor pool. Almost one-third of fetal B-progenitors are CD10-ve PreProB-progenitors, whereas, by contrast, PreProB-progenitors are almost undetectable (0.53% ± 0.24%) in adult BM. Single-cell transcriptomics and functional assays place fetal PreProB-progenitors upstream of ProB-progenitors, identifying them as the first B-lymphoid–restricted progenitor in human fetal life. Although fetal BM PreProB-progenitors and ProB-progenitors both give rise solely to B-lineage cells, they are transcriptionally distinct. As with their fetal counterparts, adult BM PreProB-progenitors give rise only to B-lineage cells in vitro and express the expected B-lineage gene expression program. However, fetal PreProB-progenitors display a distinct, ontogeny-related gene expression pattern that is not seen in adult PreProB-progenitors, and they share transcriptomic signatures with CD10-ve B-progenitor infant acute lymphoblastic leukemia blast cells. These data identify PreProB-progenitors as the earliest B-lymphoid–...
Source: Blood - Category: Hematology Authors: OByrne, S., Elliott, N., Rice, S., Buck, G., Fordham, N., Garnett, C., Godfrey, L., Crump, N. T., Wright, G., Inglott, S., Hua, P., Psaila, B., Povinelli, B., Knapp, D. J. H. F., Agraz-Doblas, A., Bueno, C., Varela, I., Bennett, P., Koohy, H., Watt, S. M. Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research
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