Figure 4. ABCA1 Invalidation Propagates Myelopoiesis and Accelerates Extramedullary Hematopoiesis on a Tet2-Deficient Background.

(A) Experimental overview. BM from Mx1-Cre⁺, Mx1-Cre⁺Abca1^fl/fl, Mx1-Cre⁺Tet2^fl/fl, and Mx1-Cre⁺Tet2^,l/flAbca1^fl/,fl mice were transplanted into lethally irradiated WT mice, and after a 5-week recovery period, the mice were injected with poly(l:C) and analyzed over a 20-week period.

(B) Modulation of Abca1 and Tet2 mRNA expression levels in the BM of the aforementioned mouse models.

(C) Quantification of the percentage of peripheral blood myeloid cells determined by hematology cell counter over the course of 20 weeks after poly (I:C) injection in recipient mice transplanted with the BM from Mx1-Cre⁺, Mx1-Cre⁺Abca1^fl/fl, Mx-Cre⁺Tet2^fl/fl, and Mx1-Cre⁺Tet^fl/fl Abca1^fl/fl mice.

(D) Peripheral blood myeloid subsets (CD115⁺Ly6C^hi and CD115⁺Ly6C^lo monocytes and CD115⁻Ly6C^hi neutrophils) were also quantified in these mice at the indicated time point

(E) Representative H&E staining of paraffin-embedded spleen sections from these mice. Original magnification × 200. Arrows indicate extensive cellular infiltrate.

(F and G) Quantification of spleen weight (F) and myeloid subsets (eosinophils, neutrophils, monocytes, and red pulp macrophages [RPMs] in the spleens (G) of recipient mice transplanted with the BM from Mx1-Cre⁺Abca1^fl/fl, Mx1-Cre⁺Tet2, and Mx1-Cre⁺Tet2^fl/fl Abca1^fl/fl mice.

(H and I) Quantification of hematopoietic stem (H) and progenitor (MEPs); Lin⁻Sca1⁻c-kit⁺CD34^hiFcγR^hi are GMP; and Lin⁻Sca1⁻c-kit⁺CD34^hi FcγR^low are CMPs.

The results are the mean ± SEMs of 5–7 animals per groups ND, not detectable. #p < 0.05 and ##p < 0.001 versus Mx1-Cre⁺ controls.