Schloss MJ, Hulsmans M, Rohde D, Lee IH, Severe N, Foy BH, Pulous FE, Zhang S, Kokkaliaris KD, Frodermann V, Courties G, Yang C, Iwamoto Y, Knudsen AS, McAlpine CS, Yamazoe M, Schmidt SP, Wojtkiewicz GR, Masson GS, Gustafsson K, Capen D, Brown D, Higgins JM, Scadden DT, Libby P, Swirski FK, Naxerova K, Nahrendorf M. 2022. B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nature immunology. 23(4):605-618. Pubmed: 35352063 DOI:10.1038/s41590-022-01165-7


Autonomic nerves control organ function through the sympathetic and parasympathetic branches, which have opposite effects. In the bone marrow, sympathetic (adrenergic) nerves promote hematopoiesis; however, how parasympathetic (cholinergic) signals modulate hematopoiesis is unclear. Here, we show that B lymphocytes are an important source of acetylcholine, a neurotransmitter of the parasympathetic nervous system, which reduced hematopoiesis. Single-cell RNA sequencing identified nine clusters of cells that expressed the cholinergic α7 nicotinic receptor (Chrna7) in the bone marrow stem cell niche, including endothelial and mesenchymal stromal cells (MSCs). Deletion of B cell-derived acetylcholine resulted in the differential expression of various genes, including Cxcl12 in leptin receptor (LepR) stromal cells. Pharmacologic inhibition of acetylcholine signaling increased the systemic supply of inflammatory myeloid cells in mice and humans with cardiovascular disease.
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

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David Scadden’s laboratory is dedicated to discovering the principles governing blood cell production, with the ultimate goal of guiding the development of therapies for blood disorders and cancer.

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