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Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic

Shovik Bandyopadhyay1,2, Michael Duffy3, Kyung Jin Ahn4

  • 1Cellular and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Biorxiv : the Preprint Server for Biology
|April 1, 2024
PubMed
Summary

This study maps the human bone marrow's non-hematopoietic cells using single-cell sequencing and spatial imaging. It reveals distinct cell niches essential for blood production and identifies changes in acute myeloid leukemia (AML).

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Area of Science:

  • Hematology
  • Cell Biology
  • Genomics

Background:

  • The bone marrow microenvironment is crucial for blood production (hematopoiesis).
  • Non-hematopoietic cells and their spatial organization in human bone marrow are poorly understood.
  • Studying these cells in humans presents significant technical challenges.

Approach:

  • Single-cell RNA sequencing (scRNA-Seq) was used to profile 29,325 non-hematopoietic bone marrow cells.
  • CO-detection by inDEXing (CODEX) multiplexed imaging analyzed over one million cells from 18 individuals (healthy and AML).
  • A novel 53-antibody panel enabled high-resolution spatial profiling.

Key Points:

  • Nine transcriptionally distinct non-hematopoietic cell subtypes were identified.
  • A hyperoxygenated arterio-endosteal niche for early myelopoiesis was discovered.
  • Early hematopoietic stem and progenitor cells occupy an adipocytic niche.

Conclusions:

  • The study presents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow.
  • Mesenchymal stromal cell (MSC) expansion and altered spatial neighborhoods were observed in acute myeloid leukemia (AML).
  • This atlas will serve as a reference for investigating cellular interactions in hematopoiesis and related diseases.