Figure 4.
Reduced engagement of ADIPOQ, KITL, and IGF1 signaling from MSCs to HSCs is predicted to sustain transcriptional changes in MA HSCs. (A) Predicted communication network to HSCs coming from all sampled BM cell types in young mice. Circle size and line weight represent the strength of the connection predicted by CellChat and color represents each cell type. (B) Ligand-receptor pairs with significant communication probability from MSCs (MSC-Adipo-1, MSC-Adipo-2, and MSC-Osteo) to HSCs in young mice. A 1-sided permutation test was used to compute P value. (C) Differential strength of the communication network to HSCs in MA mice. Red lines denote increased interaction strength and blue lines denote decreased interaction strength. Line weight represents the degree of difference between MA and young mice. (D) Differential strength of ligand-receptor interactions from MSCs to HSCs in MA compared with young mice. Dotted line denotes zero (no difference in interaction strength). (E) Expression of Adipoq, Kitl, Mdk, and Igf1 in hematopoietic and nonhematopoietic cell clusters in pooled young mice (white) and MA mice (grey). (F) Heat map representing differences in transcript expression of ligands and receptors in MA vs young hematopoietic and nonhematopoietic cell clusters. (G) Correlation between Igf1 expression and Kitl expression in Adipo-MSC-1 in individual MA mice. Each dot represents 1 mouse. Pearson correlation, nominal P values. (H) Expression of Igf1 in (left) Adipo-MSC-1, Kitlhi Adipo-MSC-1, and KitlhiCxcl12hi Adipo-MSC-1 and (right) Osteo-MSC-1, Kitlhi Osteo-MSC-1, and Kitlhi Cxcl12hi Osteo-MSC-1. (I) Experimental design to analyze CM from young (2 months) Igf1–/– and control MSCs. (J) Concentration of IGF1 in CM from control (n = 20 individual wells treated with 4-OHT isolated from 3 individual mice) and Igf1–/– (n = 15 individual wells treated with 4-OHT isolated from 3 individual mice) MSCs. (K) Concentration of KITL (left) and CXCL12 (right) in CM from control and Igf1–/– MSCs. 4-OHT, 4-hydroxytamoxifen; GMP, granulocyte macrophage progenitor; NK, natural killer; WT, wild type.

Reduced engagement of ADIPOQ, KITL, and IGF1 signaling from MSCs to HSCs is predicted to sustain transcriptional changes in MA HSCs. (A) Predicted communication network to HSCs coming from all sampled BM cell types in young mice. Circle size and line weight represent the strength of the connection predicted by CellChat and color represents each cell type. (B) Ligand-receptor pairs with significant communication probability from MSCs (MSC-Adipo-1, MSC-Adipo-2, and MSC-Osteo) to HSCs in young mice. A 1-sided permutation test was used to compute P value. (C) Differential strength of the communication network to HSCs in MA mice. Red lines denote increased interaction strength and blue lines denote decreased interaction strength. Line weight represents the degree of difference between MA and young mice. (D) Differential strength of ligand-receptor interactions from MSCs to HSCs in MA compared with young mice. Dotted line denotes zero (no difference in interaction strength). (E) Expression of Adipoq, Kitl, Mdk, and Igf1 in hematopoietic and nonhematopoietic cell clusters in pooled young mice (white) and MA mice (grey). (F) Heat map representing differences in transcript expression of ligands and receptors in MA vs young hematopoietic and nonhematopoietic cell clusters. (G) Correlation between Igf1 expression and Kitl expression in Adipo-MSC-1 in individual MA mice. Each dot represents 1 mouse. Pearson correlation, nominal P values. (H) Expression of Igf1 in (left) Adipo-MSC-1, Kitlhi Adipo-MSC-1, and KitlhiCxcl12hi Adipo-MSC-1 and (right) Osteo-MSC-1, Kitlhi Osteo-MSC-1, and Kitlhi Cxcl12hi Osteo-MSC-1. (I) Experimental design to analyze CM from young (2 months) Igf1–/– and control MSCs. (J) Concentration of IGF1 in CM from control (n = 20 individual wells treated with 4-OHT isolated from 3 individual mice) and Igf1–/– (n = 15 individual wells treated with 4-OHT isolated from 3 individual mice) MSCs. (K) Concentration of KITL (left) and CXCL12 (right) in CM from control and Igf1–/– MSCs. 4-OHT, 4-hydroxytamoxifen; GMP, granulocyte macrophage progenitor; NK, natural killer; WT, wild type.

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