Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis
- University of Bonn, Germany
- Universitätsklinikum Erlangen, Germany
- German Center for Neurodegenerative Diseases, Germany
Abstract
During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.
Data availability
RNA-seq data from bulk and single-cell experiments are available under GEO accession number GSE225444. Source data for CODEX pictures (raw .tiff files) and analyses are available as pyramidal file at Dryad (Mass, Elvira (2023), Source Data Kayvanjoo et al., Dryad, Dataset, https://doi.org/10.5061/dryad.fn2z34v00). Due to size restrictions, the original CODEX .czi files could not be uploaded, but will be made available without restrictions after contacting the corresponding author.
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Source Data Kayvanjoo et al. CODEX of fetal livers at E14.5Dryad Digital Repository, doi:10.5061/dryad.fn2z34v00.
Article and author information
Author details
Amir Hossein Kayvanjoo
Funding
Deutsche Forschungsgemeinschaft (EXC2151-390873048)
- Joachim L Schultze
- Eva Kiermaier
- Marc Beyer
- Andreas Schlitzer
- Elvira Mass
Deutsche Forschungsgemeinschaft (505539112)
- Stefan Uderhardt
Hightech Agenda Bavaria
- Stefan Uderhardt
Horizon 2020 Framework Programme (101039438)
- Stefan Uderhardt
Deutsche Forschungsgemeinschaft (GRK2168)
- Katharina Mauel
- Elvira Mass
Deutsche Forschungsgemeinschaft (GRK1873/2)
- Elvira Mass
Deutsche Forschungsgemeinschaft (SFB1454)
- Joachim L Schultze
- Marc Beyer
- Andreas Schlitzer
- Elvira Mass
Deutsche Forschungsgemeinschaft (FOR5547 - Project-ID 503306912)
- Elvira Mass
Boehringer Ingelheim Stiftung
- Katharina Mauel
Horizon 2020 Framework Programme (851257)
- Elvira Mass
Deutsche Forschungsgemeinschaft (448121430)
- Stefan Uderhardt
Deutsche Forschungsgemeinschaft (405969122)
- Stefan Uderhardt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Florent Ginhoux, Singapore Immunology Network, Singapore
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations of the LANUV and Veterinary Office of the City of Bonn. All of the animals were handled according to approved institutional animal care at the LIMES GRC. The protocol was approved by the LANUV (Permit Number: 2018.A056).
Version history
- Received: January 29, 2023
- Preprint posted: February 23, 2023 (view preprint)
- Accepted: March 23, 2024
- Accepted Manuscript published: March 25, 2024 (version 1)
- Version of Record published: April 10, 2024 (version 2)
Copyright
© 2024, Kayvanjoo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis
eLife 13:e86493.
https://doi.org/10.7554/eLife.86493
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