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.
-
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.
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).
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.
Metrics
-
- 2,409
- views
-
- 353
- downloads
-
- 12
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis
eLife 13:e86493.
https://doi.org/10.7554/eLife.86493
Further reading
-
- Developmental Biology
Wing dimorphism is a common phenomenon that plays key roles in the environmental adaptation of aphid; however, the signal transduction in response to environmental cues and the regulation mechanism related to this event remain unknown. Adenosine (A) to inosine (I) RNA editing is a post-transcriptional modification that extends transcriptome variety without altering the genome, playing essential roles in numerous biological and physiological processes. Here, we present a chromosome-level genome assembly of the rose-grain aphid Metopolophium dirhodum by using PacBio long HiFi reads and Hi-C technology. The final genome assembly for M. dirhodum is 447.8 Mb, with 98.50% of the assembled sequences anchored to nine chromosomes. The contig and scaffold N50 values are 7.82 and 37.54 Mb, respectively. A total of 18,003 protein-coding genes were predicted, of which 92.05% were functionally annotated. In addition, 11,678 A-to-I RNA-editing sites were systematically identified based on this assembled M. dirhodum genome, and two synonymous A-to-I RNA-editing sites on CYP18A1 were closely associated with transgenerational wing dimorphism induced by crowding. One of these A-to-I RNA-editing sites may prevent the binding of miR-3036-5p to CYP18A1, thus elevating CYP18A1 expression, decreasing 20E titer, and finally regulating the wing dimorphism of offspring. Meanwhile, crowding can also inhibit miR-3036-5p expression and further increase CYP18A1 abundance, resulting in winged offspring. These findings support that A-to-I RNA editing is a dynamic mechanism in the regulation of transgenerational wing dimorphism in aphids and would advance our understanding of the roles of RNA editing in environmental adaptability and phenotypic plasticity.
-
- Developmental Biology
The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature deformation of touch neurons and impaired touch responses in a yap-1/YAP-dependent manner, the downstream transcriptional co-activator of LATS. Decreased movement as well as microtubule destabilization by treatment with colchicine or disruption of microtubule-stabilizing genes alleviated the neuronal deformation of wts-1 mutants. Colchicine exerted neuroprotective effects even during normal aging. In addition, the deficiency of a microtubule-severing enzyme spas-1 also led to precocious structural deformation. These results consistently suggest that hyper-stabilized microtubules in both wts-1-deficient neurons and normally aged neurons are detrimental to the maintenance of neuronal structural integrity. In summary, Hpo pathway governs the structural and functional maintenance of differentiated neurons by modulating microtubule stability, raising the possibility that the microtubule stability of fully developed neurons could be a promising target to delay neuronal aging. Our study provides potential therapeutic approaches to combat age- or disease-related neurodegeneration.
