The first bone marrow atlas in mice has been created, which could pave the way for the production of specific blood cells at will, it has been announced.
Scientists at the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s Hospital Medical Center, Ohio, USA, used a combination of cell-by-cell analysis techniques to build a 3D atlas of bone marrow tissue. They say their work will advance scientific understanding of how the organisation of tiny blood vessels in the bone marrow regulates how blood gets produced.
Senior author Dr Daniel Lucas said: “We finally have the tools to directly observe bone marrow cell differentiation. These results show that the bone marrow is a highly organised tissue and that this organisation is provided by specific subsets of vessels.
“This is telling us that the organisation of the vasculature dictates blood production. If we determine how the vessels function we will be one step closer to controlling the production of specific blood cells at will.”
Writing in the journal Nature, the authors describe developing novel confocal imaging methods for unprecedented resolution of blood cells in the bone marrow of mice.
Until now, tracing the lineage of cell types during stages of development required destroying the tissue. However, in this project the team developed methods that, for the first time, could image and trace unique blood progenitors without destroying the tissue structure.
“Tracking these special cell clusters revealed new information about the structure of bone marrow, including the insight that the bone marrow has a surprising degree of organisation and that specific blood vessels support the production of unique blood cell types,” said Dr Lucas.
The team found that two different progenitor cells – one that produces granulocytes and another that produces monocytes and dendritic cells – localise to different blood-vessel structures known as sinusoids.
The authors, who include scientists from Cincinnati Children's and the University of Cincinnati, as well as colleagues in Colorado, Texas and Michigan, believe the atlas could one day be used to help develop highly customised blood cell factories that would mimic bone marrow function in laboratory settings.
These blood organoids could be used to produce populations of blood cells with specific genetic variations, which scientists could analyse to develop improved treatments for disease.
It could also mean blood organoids might become a form of treatment themselves, by enabling doctors to replace a patient's diseased cells with gene-edited healthy cells that face no risk of rejection.
“This certainly has implications for generating blood organoids,” continued Dr Lucas. “The groups working on blood organoids have been trying to produce organoids that can maintain or expand stem cell production. Our data indicates that additional structures are needed to produce mature blood cells in a balanced manner. We want to be able to visualise every step in the production of the different types of blood cells.”
Zhang J, Wu Q, Johnson CB, Pham G, Kinder JM, Olsson A, Slaughter A, May M, Weinhaus B, D'Alessandro A, Engel JD, Jiang JX, Kofron JM, Huang LF, Prasath VBS, Way SS, Salomonis N, Grimes HL, Lucas D (2021) “In situ mapping identifies distinct vascular niches for myelopoiesis.” Nature, doi: 10.1038/s41586-021-03201-2
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