Skip to main content

The maternal-fetal interface is an early hematopoietic niche enriched in distinct erythro-myeloid progenitors.

Nature immunology

Authors: Rohit Jain, Shweta Tikoo, Carlos Márquez-Burgoa, Stephanie A Gerhofer, Brendon Martinez, Mariagiovanna Barresi, Dörte Symmank, Minoo Ghannadan, Barbara Öhler, Anna-Lena Höbler, Rafael de Freitas E Silva, Dirk Baumjohann, Susanne Feil, Robert Feil, Sylvia Knapp, Philipp Starkl, Wilfried Ellmeier, Steffen Jung, Jürgen Pollheimer, Stuart T Fraser, Wolfgang Weninger

Embryonic hematopoiesis is thought to occur exclusively in the extraembryonic yolk sac before hematopoietic stem cells (HSCs) arise in the aorta-gonad-mesonephros region. Here we identify a previously unrecognized hematopoietic site at the maternal-fetal interface in mice, termed MIXER (Maternally Interfaced eXtraEmbRyonic) tissue, which develops contemporaneously with the yolk sac and exhibits robust hematopoietic activity. MIXER contains abundant hematopoietic precursors, including classical CSF1R erythro-myeloid progenitors and a unique embryonic CD4CSF1R Erythro-Myeloid PRogenitOR (eEMPROR) population. Lineage-tracing experiments demonstrate that eEMPROR cells contribute to select macrophage subpopulations during fetal development, primarily in the perivascular space. Notably, early human placental villi, before HSC emergence, also harbor CD4 nucleated erythrocytes, indicating a conserved hematopoietic role for the maternal-fetal interface. These findings establish MIXER as an anatomically distinct niche for embryonic hematopoiesis and expand the developmental map of blood cell emergence in mammals.

© 2026. The Author(s).

PMID: 42934291

Participating cluster members