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Peer-reviewedCC BY 4.0Nature Immunology

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

  • Rohit Jain1,2,3
  • Shweta Tikoo1,2,3
  • Carlos Márquez-Burgoa1
  • Stephanie A. Gerhofer1
  • Brendon Martinez2
  • Mariagiovanna Barresi4
  • Dörte Symmank1
  • Minoo Ghannadan1
  • Barbara Öhler5
  • Anna-Lena Höbler5
  • Rafael de Freitas e Silva6
  • Dirk Baumjohann7
9 more authors
  • Susanne Feil4
  • Robert Feil4
  • Sylvia Knapp8
  • Philipp Starkl8
  • Wilfried Ellmeier6
  • Steffen Jung9
  • Jürgen Pollheimer5
  • Stuart T. Fraser10,11
  • Wolfgang Weninger1,2,3
11 affiliations
  1. 1Department of Dermatology, Medical University of Vienna, Vienna, Austria
  2. 2Centenary Institute, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales Australia
  3. 3Sydney Medical School, University of Sydney, Camperdown, New South Wales Australia
  4. 4Interfakultäres Institut für Biochemie (IFIB), Universität Tübingen, Tübingen, Germany
  5. 5Department of Obstetrics and Gynecology, Reproductive Biology Unit, Maternal–Fetal Immunology Group, Medical University of Vienna, Vienna, Austria
  6. 6Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
  7. 7Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany
  8. 8Research Division of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
  9. 9Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel
  10. 10School of Medical Sciences, University of Sydney, Sydney, New South Wales Australia
  11. 11University of Sydney Nano Institute, University of Sydney, Sydney, New South Wales Australia
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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.

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Cite

BibTeXRIS
BibTeX
@article{jain2026maternalfetal,
  title = {{The maternal–fetal interface is an early hematopoietic niche enriched in distinct erythro-myeloid progenitors}},
  author = {Rohit Jain and Shweta Tikoo and Carlos Márquez-Burgoa and Stephanie A. Gerhofer and Brendon Martinez and Mariagiovanna Barresi and Dörte Symmank and Minoo Ghannadan and Barbara Öhler and Anna-Lena Höbler and Rafael de Freitas e Silva and Dirk Baumjohann and Susanne Feil and Robert Feil and Sylvia Knapp and Philipp Starkl and Wilfried Ellmeier and Steffen Jung and Jürgen Pollheimer and Stuart T. Fraser and Wolfgang Weninger},
  journal = {Nature Immunology},
  year = {2026},
  month = oct,
  doi = {10.1038/s41590-026-02683-4},
  url = {https://doi.org/10.1038/s41590-026-02683-4},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The maternal–fetal interface is an early hematopoietic niche enriched in distinct erythro-myeloid progenitors
AU  - Rohit Jain
AU  - Shweta Tikoo
AU  - Carlos Márquez-Burgoa
AU  - Stephanie A. Gerhofer
AU  - Brendon Martinez
AU  - Mariagiovanna Barresi
AU  - Dörte Symmank
AU  - Minoo Ghannadan
AU  - Barbara Öhler
AU  - Anna-Lena Höbler
AU  - Rafael de Freitas e Silva
AU  - Dirk Baumjohann
AU  - Susanne Feil
AU  - Robert Feil
AU  - Sylvia Knapp
AU  - Philipp Starkl
AU  - Wilfried Ellmeier
AU  - Steffen Jung
AU  - Jürgen Pollheimer
AU  - Stuart T. Fraser
AU  - Wolfgang Weninger
PY  - 2026
DA  - 2026/10/26
JO  - Nature Immunology
DO  - 10.1038/s41590-026-02683-4
UR  - https://doi.org/10.1038/s41590-026-02683-4
AB  - 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.
SN  - 1529-2908
SN  - 1529-2916
ER  -