Secondary bile acids function through the vitamin D receptor in myeloid progenitors to promote myelopoiesis

Brandon Thompson, Shan Lu, Julio Revilla, Md Jashim Uddin, David N. Oakland, Savannah Brovero, Sunduz Keles, Emery H. Bresnick, William A. Petri, Stacey L. Burgess

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Metabolic products of the microbiota can alter hematopoiesis. However, the contribution and site of action of bile acids is poorly understood. Here, we demonstrate that the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), increase bone marrow myelopoiesis. Treatment of bone marrow cells with DCA and LCA preferentially expanded immunophenotypic and functional colony-forming unit granulocyte and macrophage (CFU-GM) granulocyte-monocyte progenitors (GMPs). DCA treatment of sorted hematopoietic stem and progenitor cells (HSPCs) increased CFU-GMs, indicating that direct exposure of HSPCs to DCA sufficed to increase GMPs. The vitamin D receptor (VDR) was required for the DCA-induced increase in CFU-GMs and GMPs. Single-cell RNA sequencing revealed that DCA significantly upregulated genes associated with myeloid differentiation and proliferation in GMPs. The action of DCA on HSPCs to expand GMPs in a VDR-dependent manner suggests microbiome-host interactions could directly affect bone marrow hematopoiesis and potentially the severity of infectious and inflammatory disease.

Original languageEnglish (US)
Pages (from-to)4970-4982
Number of pages13
JournalBlood Advances
Volume7
Issue number17
DOIs
StatePublished - Sep 12 2023

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Secondary bile acids function through the vitamin D receptor in myeloid progenitors to promote myelopoiesis'. Together they form a unique fingerprint.

Cite this