EKLF/KLF1 expression defines a unique macrophage subset during mouse erythropoiesis
- Mount Sinai School of Medicine, United States
Abstract
Erythroblastic islands are a specialized niche that contain a central macrophage surrounded by erythroid cells at various stages of maturation. However, identifying the precise genetic and transcriptional control mechanisms in the island macrophage remains difficult due to macrophage heterogeneity. Using unbiased global sequencing and directed genetic approaches focused on early mammalian development, we find that fetal liver macrophage exhibit a unique expression signature that differentiates them from erythroid and adult macrophage cells. The importance of EKLF/KLF1 in this identity is shown by expression analyses in EKLF-/- and in EKLF-marked macrophage cells. Single cell sequence analysis simplifies heterogeneity and identifies clusters of genes important for EKLF-dependent macrophage function and novel cell surface biomarkers. Remarkably, this singular set of macrophage island cells appears transiently during embryogenesis. Together these studies provide a detailed perspective on the importance of EKLF in establishment of the dynamic gene expression network within erythroblastic islands in the developing embryo and provide the means for their efficient isolation.
Data availability
Data deposite in GEO, accession number: GSE156153, Source data are included for Figures 1,3,4,5,6.
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EKLF/Klf1 expression specifies a unique macrophage subset during mouse erythropoiesisNCBI Gene Expression Omnibus, GSE156153.
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Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironmentNCBI Gene Expression Omnibus, GSE63340.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK102260)
- James J Bieker
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK121671)
- James J Bieker
National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK115686)
- Merlin Nithya Gnanapragasam
Black Family Stem Cell Institute (Postdoctoral award)
- Kaustav Mukherjee
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 in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#18-1911) of the Mount Sinai School of Medicine.
Copyright
© 2021, Mukherjee 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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EKLF/KLF1 expression defines a unique macrophage subset during mouse erythropoiesis
eLife 10:e61070.
https://doi.org/10.7554/eLife.61070
Further reading
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