Hierarchical stem cell topography splits growth and homeostatic functions in the fish gill
- Centre for Organismal Studies, Heidelberg University, Germany
- Heidelberg University, Germany
- Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Spain
- Murdoch Children's Research Institute, Royal Children's Hospital, Australia
- National Institute for Basic Biology, National Institutes of Natural Sciences, Japan
Abstract
While lower vertebrates contain adult stem cells (aSCs) that maintain homeostasis and drive un-exhaustive organismal growth, mammalian aSCs display mainly the homeostatic function. Here we use lineage analysis in the fish gill to address aSCs and report separate stem cell populations for homeostasis and growth. These aSCs are fate-restricted during the entire post-embryonic life and even during re-generation paradigms. We use chimeric animals to demonstrate that p53 mediates growth coordination among fate-restricted aSCs, suggesting a hierarchical organisation among lineages in composite organs like the fish gill. Homeostatic and growth aSCs are clonal but differ in their topology; modifications in tissue architecture can convert the homeostatic zone into a growth zone, indicating a leading role for the physical niche defining stem cell output. We hypothesise that physical niches are main players to restrict aSCs to a homeostatic function in animals with fixed adult size.
Data availability
All data analysed for this study is included in the manuscript and supporting files. Raw sequencing data have been deposited in GEO under accession code GSE130939
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Transcriptome analysts of a growth domain and a differentiated domain of the medaka gillNCBI Gene Expression Omnibus, GSE130939.
Article and author information
Author details
Elizabeth Mayela Ambrosio
Diana-Patricia Danciu
Juan R Martínez-Morales
Anna Marciniak-Czochra
Funding
Deutsche Forschungsgemeinschaft (SFB873/A11)
- Lazaro Centanin
Deutsche Forschungsgemeinschaft (SFB873/B08)
- Anna Marciniak-Czochra
University of Melbourne (Melbourne Research Fellowship / Graduate Student Fellowship)
- Julian Stopler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alejandro Sánchez Alvarado, Stowers Institute for Medical Research, United States
Ethics
Animal experimentation: Experimental procedures with fish were performed in accordance with the German animal welfare law and approved by the local government (Tierschutzgesetz {section sign}11, Abs. 1, Nr. 1, husbandry permit number AZ 35-9185.64/BH; line generation permit number AZ 35-9185.81/G-145-15), and with the approval from the Institutional Animal Care and Use Committees of the National Institute for Basic Biology, Japan.
Version history
- Received: November 19, 2018
- Accepted: May 14, 2019
- Accepted Manuscript published: May 15, 2019 (version 1)
- Accepted Manuscript updated: May 16, 2019 (version 2)
- Version of Record published: May 24, 2019 (version 3)
Copyright
© 2019, Stolper 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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Hierarchical stem cell topography splits growth and homeostatic functions in the fish gill
eLife 8:e43747.
https://doi.org/10.7554/eLife.43747
Further reading
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- Developmental Biology
- Neuroscience
Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4–82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.
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- Developmental Biology
- Immunology and Inflammation
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.
