RSPO3 is expressed by LepR⁺stromal cells in the bone marrow. (A) A t-distributed stochastic neighbor embedding (t-SNE) plot with color-coded clusters of various bone marrow–derived cells is shown. t-SNE plots of various bone marrow–derived cell populations with color-coded expression levels of Rspo2 (B) and Rspo3 (C). (D) Markov Affinity-based Graph Imputation of Cells (MAGIC) plot showing co-expression of Rspo2 and Rspo3 with Lepr in a subset of bone marrow cells. (E) t-SNE plot of bone marrow–derived osteoblasts (Col2.3⁺), perivascular cells (Lepr⁺), and vascular endothelial cells (VE-cad⁺) from Tikhonova et al⁴⁰ with color-coded expression levels of Rspo3. (F) Representative image of an ISH for Rspo3 transcript distribution in the bone marrow of n = 3 animals. Rectangles mark regions shown at higher magnification; arrows point out Rspo3 transcripts near blood vessels (BV). (G) Representative image of a double ISH for Rspo3 (blue) and Lepr (red) transcript distribution in the bone marrow of n = 3 animals. (H) Hierarchical clustering of human hematopoietic progenitor populations from the Immunological Genome Project data set⁴¹ based on the expression profile of common Wnt receptors. Expression data are scaled column-wise for each gene across cell types. Scale bars, 100 μm (panel F, large panel) and 50 μm (panel F, smaller panels; panel G). DC, dendritic cells; Ery/Meg prog, erythroid-megakaryocytic progenitors; Fbl, fibroblasts; l. pre-B, large pre–B cells; LMPPs, lymphoid-primed multipotent progenitors; max, maximum; min, minimum; MSC, mesenchymal stromal cells; NK, natural killer cells; prog, progenitor; s. pre-B, small pre–B cells; T, T cells.