Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs

Miguel Ganuza, Ashley Chabot, Xing Tang, Wenjian Bi, Sivaraman Natarajan, Robert Carter, Charles Gawad, Guolian Kang, Yong Cheng and Shannon McKinney-Freeman ()
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Miguel Ganuza: St. Jude Children’s Research Hospital
Ashley Chabot: St. Jude Children’s Research Hospital
Xing Tang: St. Jude Children’s Research Hospital
Wenjian Bi: St. Jude Children’s Research Hospital
Sivaraman Natarajan: St. Jude Children’s Research Hospital
Robert Carter: St. Jude Children’s Research Hospital
Charles Gawad: St. Jude Children’s Research Hospital
Guolian Kang: St. Jude Children’s Research Hospital
Yong Cheng: St. Jude Children’s Research Hospital
Shannon McKinney-Freeman: St. Jude Children’s Research Hospital

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. The same developmental origin makes it difficult to identify specific markers that discern between an intraembryonic versus YS-origin using a lineage trace approach. Additionally, the highly migratory nature of blood cells and the inability of pre-circulatory embryonic cells (i.e., 5–7 somite pairs (sp)) to robustly engraft in transplantation, even after culture, has precluded scientists from properly answering these questions. Here we report robust, multi-lineage and serially transplantable dHSC activity from cultured 2–7sp murine embryonic explants (Em-Ex). dHSC are undetectable in 2–7sp YS explants. Additionally, the engraftment from Em-Ex is confined to an emerging CD31+CD45+c-Kit+CD41− population. In sum, our work supports a model in which the embryo, not the YS, is the major source of lifelong definitive hematopoiesis.

Date: 2018
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DOI: 10.1038/s41467-018-07769-8

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