1. Developmental Biology
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EKLF/KLF1 expression defines a unique macrophage subset during mouse erythropoiesis

  1. Kaustav Mukherjee
  2. Li Xue
  3. Antanas Planutis
  4. Merlin Nithya Gnanapragasam
  5. Andrew Chess
  6. James J Bieker  Is a corresponding author
  1. Mount Sinai School of Medicine, United States
Research Article
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Cite this article as: eLife 2021;10:e61070 doi: 10.7554/eLife.61070

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.

Article and author information

Author details

  1. Kaustav Mukherjee

    Cell, Developmental, and Regenerative Biology, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Li Xue

    Cell, Developmental, and Regenerative Biology, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Antanas Planutis

    Cell, Developmental, and Regenerative Biology, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Merlin Nithya Gnanapragasam

    Cell, Developmental, and Regenerative Biology, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew Chess

    Cell, Developmental, and Regenerative Biology, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. James J Bieker

    Cell, Developmental, and Regenerative Biology, Mount Sinai School of Medicine, New York, United States
    For correspondence
    james.bieker@mssm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5128-7476

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.

Reviewing Editor

  1. Florent Ginhoux, Agency for Science Technology and Research, Singapore

Publication history

  1. Received: July 14, 2020
  2. Accepted: February 10, 2021
  3. Accepted Manuscript published: February 11, 2021 (version 1)
  4. Version of Record published: March 4, 2021 (version 2)

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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