Open AccessYolk sac, but not hematopoietic stem cell–derived progenitors, sustain erythropoiesis throughout murine embryonic life
Author(s) -
Francisca Soares-da-Silva,
Laina Freyer,
Ramy Elsaid,
Odile Burlen-Defranoux,
Lorea Iturri,
Odile Sismeiro,
Perpétua Pinto-do-Ó,
Elisa Gomez Perdiguero,
Ana Cumano
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20201729
Subject(s) - yolk sac , biology , haematopoiesis , stem cell , embryonic stem cell , microbiology and biotechnology , progenitor cell , erythropoiesis , stem cell factor , immunology , erythropoietin , hemangioblast , embryo , medicine , endocrinology , genetics , anemia , gene
In the embryo, the first hematopoietic cells derive from the yolk sac and are thought to be rapidly replaced by the progeny of hematopoietic stem cells. We used three lineage-tracing mouse models to show that, contrary to what was previously assumed, hematopoietic stem cells do not contribute significantly to erythrocyte production up until birth. Lineage tracing of yolk sac erythromyeloid progenitors, which generate tissue resident macrophages, identified highly proliferative erythroid progenitors that rapidly differentiate after intra-embryonic injection, persisting as the major contributors to the embryonic erythroid compartment. We show that erythrocyte progenitors of yolk sac origin require 10-fold lower concentrations of erythropoietin than their hematopoietic stem cell-derived counterparts for efficient erythrocyte production. We propose that, in a low erythropoietin environment in the fetal liver, yolk sac-derived erythrocyte progenitors efficiently outcompete hematopoietic stem cell progeny, which fails to generate megakaryocyte and erythrocyte progenitors.