The maternal–fetal interface is an early hematopoietic niche enriched in distinct erythro-myeloid progenitors
Abstract 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 CD4 + CSF1R − 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.
Authors
- Susanne C. Feil (ORCID: https://orcid.org/0000-0003-2148-8773)
- Rafael de Freitas e Silva (ORCID: https://orcid.org/0000-0001-7343-5986)
- Wilfried Ellmeier (ORCID: https://orcid.org/0000-0001-8192-8481)
- Philipp M. Starkl (ORCID: https://orcid.org/0000-0001-7521-129X)
- Stuart T. Fraser (ORCID: https://orcid.org/0000-0003-3795-9461)
- Anna-Lena Höbler (ORCID: https://orcid.org/0000-0001-5529-9378)
- Barbara Öhler (ORCID: https://orcid.org/0009-0008-2360-0670)
- Minoo Ghannadan
- Dörte Symmank (ORCID: https://orcid.org/0000-0002-3992-6447)
- Sylvia Knapp (ORCID: https://orcid.org/0000-0001-9016-5244)
- Shweta Tikoo (ORCID: https://orcid.org/0000-0001-5850-8075)
- Robert Feil (ORCID: https://orcid.org/0000-0002-7335-4841)
- Wolfgang Weninger (ORCID: https://orcid.org/0000-0003-3133-8699)
- Dirk Baumjohann (ORCID: https://orcid.org/0000-0001-8385-8288)
- Steffen Jung (ORCID: https://orcid.org/0000-0003-4290-5716)
- Brendon Martinez (ORCID: https://orcid.org/0000-0001-6026-812X)
- Mariagiovanna Barresi (ORCID: https://orcid.org/0000-0002-5297-8356)
- Jain Rohit (ORCID: https://orcid.org/0000-0002-4905-462X)
- Jürgen Pollheimer
- Carlos Márquez-Burgoa (ORCID: https://orcid.org/0009-0004-1433-6186)
- Stephanie A. Gerhofer (ORCID: https://orcid.org/0009-0004-3944-3017)
Institutions
- The University of Sydney (AU)
- University of Bonn (DE)
- University Hospital Bonn (DE)
- Centenary Institute (AU)
- Weizmann Institute of Science (IL)
- Medical University of Vienna (AT)
- University of Tübingen (DE)
Publication Details
- Journal
- Nature Immunology
- Published
- 2026-10-26
- DOI
- https://doi.org/10.1038/s41590-026-02683-4
- Citations
- 2
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 10.00