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Eomes expression identifies the early bone marrow precursor to classical NK cells.

Zhitao Liang1,2, Hope D Anderson3, Veronica Locher1

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|June 13, 2024
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Summary
This summary is machine-generated.

Researchers identified EomeshiNKneg cells as the bone marrow precursor to natural killer (NK) cells. These findings reveal that NK cells and type 1 innate lymphoid cells (ILC1s) diverged early in development.

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Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • Natural killer (NK) cells are cytotoxic lymphocytes crucial for immunity against pathogens and tumors.
  • Type 1 innate lymphoid cells (ILC1s) share cytokine production with NK cells but reside in tissues and lack cytotoxicity.
  • The developmental relationship between NK cells and ILC1s remains unclear, with possibilities including distinct lineages or shared precursors.

Purpose of the Study:

  • To investigate the developmental origins of NK cells and ILC1s.
  • To identify precursor populations that give rise to NK cells and ILC1s.
  • To determine if NK cells and ILC1s arise from a common progenitor or separate lineages.

Main Methods:

  • Single-cell RNA sequencing was employed to analyze cell populations.
  • Flow cytometry was used to characterize cell surface markers and transcription factor expression.
  • In vivo cell transfer experiments were conducted using Rag2-/-Il2rg-/- recipient mice.

Main Results:

  • A distinct population of bone marrow lineage-negative, NK receptor-negative cells expressing high levels of the transcription factor Eomes (EomeshiNKneg) was identified.
  • Transfer of EomeshiNKneg cells into immunodeficient recipients generated functional NK cells that exhibited anti-metastatic activity.
  • Transfer of PLZF+ ILC precursors generated a mix of ILC subsets (ILC1s, ILC2s, ILC3s) lacking cytotoxic function.

Conclusions:

  • EomeshiNKneg cells represent the specific bone marrow precursor for classical NK cells.
  • The study provides evidence that the NK cell and ILC1 lineages diverge early in development.
  • This research clarifies the developmental trajectory of innate lymphoid cells and NK cells.