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@article{O'Byrne:2019:10.1182/blood.2019001289,
author = {O'Byrne, S and Elliott, N and Rice, S and Buck, G and Fordham, N and Garnett, C and Godfrey, L and Crump, NT and Wright, G and Inglott, S and Hua, P and Psaila, B and Povinelli, B and Knapp, DJHF and Agraz-Doblas, A and Bueno, C and Varela, I and Bennett, P and Koohy, H and Watt, SM and Karadimitris, A and Mead, AJ and Ancliff, P and Vyas, P and Menendez, P and Milne, TA and Roberts, I and Roy, A},
doi = {10.1182/blood.2019001289},
journal = {Blood},
pages = {1059--1071},
title = {Discovery of a CD10 negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs},
url = {http://dx.doi.org/10.1182/blood.2019001289},
volume = {134},
year = {2019}
}

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TY  - JOUR
AB  - Human lymphopoiesis is a dynamic life-long process that starts in utero 6 weeks post-conception. Fetal B-lymphopoiesis remains poorly defined and yet is key to understanding leukemia initiation in early life. Here, we provide a comprehensive analysis of the human fetal B-cell developmental hierarchy. We report the presence in fetal tissues of two 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- and ProB-progenitors appear early in the first trimester in embryonic liver, followed by a sustained second wave of B-progenitor development in fetal BM, where together they form >40% of the total HSC/progenitor pool. Almost one-third of fetal B-progenitors are CD10-ve PreProB-progenitors while, by contrast, PreProB-progenitors are almost undetectable (0.53{plus minus}0.24%) in adult BM. Single-cell transcriptomics and functional assays place fetal PreProB- upstream of ProB-progenitors, identifying them as the first B-lymphoid restricted progenitor in human fetal life. Fetal BM PreProB- and ProB-progenitors both give rise solely to B-lineage cells yet they are transcriptionally distinct. Like 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 which is not seen in adult PreProB-progenitors; and share transcriptomic signatures with CD10-ve B-progenitor infant acute lymphoblastic leukemia blast cells. These data identify PreProB-progenitors as the earliest B-lymphoid-restricted progenitor in human fetal life, and suggest that this fetal-restricted committed B-progenitor might provide a permissive cellular context for prenatal B-progenitor leukemia initiation.
AU  - O'Byrne,S
AU  - Elliott,N
AU  - Rice,S
AU  - Buck,G
AU  - Fordham,N
AU  - Garnett,C
AU  - Godfrey,L
AU  - Crump,NT
AU  - Wright,G
AU  - Inglott,S
AU  - Hua,P
AU  - Psaila,B
AU  - Povinelli,B
AU  - Knapp,DJHF
AU  - Agraz-Doblas,A
AU  - Bueno,C
AU  - Varela,I
AU  - Bennett,P
AU  - Koohy,H
AU  - Watt,SM
AU  - Karadimitris,A
AU  - Mead,AJ
AU  - Ancliff,P
AU  - Vyas,P
AU  - Menendez,P
AU  - Milne,TA
AU  - Roberts,I
AU  - Roy,A
DO  - 10.1182/blood.2019001289
EP  - 1071
PY  - 2019///
SN  - 0006-4971
SP  - 1059
TI  - Discovery of a CD10 negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood.2019001289
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31383639
UR  - http://hdl.handle.net/10044/1/73566
VL  - 134
ER  -

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