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Advanced Imaging Technique Describes the in vivo Anatomy of Myelopoiesis

Review of “In situ mapping identifies distinct vascular niches for myelopoiesis” from Nature by Stuart P. Atkinson

Hematopoietic stem cells (HSCs) and multipotent progenitor cells differentiate within the bone marrow to form the lineage-specific progenitors that generate all major lineages of blood cells. However, given our inability to uniquely identify myeloid cells based on morphology, we know unfortunately little regarding the “anatomy” of myelopoiesis and the supporting structures.

In a huge step forward in this research field, researchers led by Daniel Lucas (Cincinnati Children’s Medical Center, Cincinnati, OH, USA) now describe the development of novel imaging approaches that supported the generation of “atlases” that describe the differentiation of granulocytes, monocytes, and dendritic cells. Overall, the findings reported in their newly published study [1] highlight a crucial role for local cues from distinct blood vessels in the spatial organization of definitive blood cell differentiation.

Zhang et al. developed three antibody stains that permitted the examination of myelopoiesis through imaging by explicitly identifying the spatial layout of the various lineages of progenitors and terminally differentiated cell types downstream of the common myeloid progenitor.

The highlights of this paper include:

  • The identification of distinct blood-vessel structures known as “sinusoids” with lineage-specific spatial and clonal architectures as the sites of generation for granulocytes and dendritic cells/monocytes
  • The induction of progenitor cell self-renewal in lineage-specific progenitor clusters following acute systemic bacterial infection
    • Notably, the distinct lineages remain spatially separated
  • The collocation of monocyte-dendritic progenitors with non-classical monocytes and dendritic cells to blood vessels that express colony-stimulating factor 1 (CSF1), a major regulator of myelopoiesis
    • Endothelial-specific deletion of Csf1 disrupts both the architecture surrounding the monocyte-dendritic progenitors and their localization to sinusoids
    • This effect reduces the number of monocyte-dendritic progenitors and their ability to differentiate, which subsequently prompts a loss of non-classical monocytes and dendritic cells

The findings of this truly fascinating new study indicate that local cues produced by distinct blood vessels help to spatially organize definitive myeloid differentiation and provide a new conceptual framework towards a better understanding of differentiation, the dissection of disease-associated myelopoiesis, and the design of optimized organ systems with the potential to produce multilineage blood cells ex vivo.

For more on the power of this new imaging system and all the details about the spatial organization of the bone marrow, stay tuned to the Stem Cells Portal!

References

  1. Zhang J, Wu Q, Johnson CB, et al., In situ mapping identifies distinct vascular niches for myelopoiesis. Nature 2021;590:457-462.