MO disrupts hemoglobin switching and heme biosynthesis in fetal erythroid cells. (A) Schematic overview of α- and β-globin gene clusters and their developmental expression patterns in mice and humans. (B) Hemoglobin switching dynamics from embryonic to adult forms in mouse embryos (E9.5-E17.5). (C-E) Bar plots show α- and β-globin composition in mouse placenta with yolk sac (EryPs), embryonic liver (EryDs), and human UCB erythroid cells (nRBCs). (F-H) Expression levels of globin genes in EryPs, EryDs, and nRBCs. (I) Schematic diagram illustrating iron transport and mitochondrial heme biosynthesis pathways. (J-L) Expression of key genes involved in iron transportation (TFRC/Tfrc, SLC11A2/Slc11a2, and SLC25A37/Slc25a37) and heme biosynthesis (ALAS2/Alas2, HMBS/Hmbs, UROS/Uros, UROD/Urod, CPOX/Cpox, PPOX/Ppox, and FECH/Fech) in EryPs, EryDs, and nRBCs. The scRNA-seq analyses were based on 3 pregnancies per group for mouse tissues (3 embryos per pregnancy) and 4 lean vs 3 obese samples for human UCB. Statistical significance was determined using the Wilcoxon rank-sum test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.
Figure 7.

MO disrupts hemoglobin switching and heme biosynthesis in fetal erythroid cells. (A) Schematic overview of α- and β-globin gene clusters and their developmental expression patterns in mice and humans. (B) Hemoglobin switching dynamics from embryonic to adult forms in mouse embryos (E9.5-E17.5). (C-E) Bar plots show α- and β-globin composition in mouse placenta with yolk sac (EryPs), embryonic liver (EryDs), and human UCB erythroid cells (nRBCs). (F-H) Expression levels of globin genes in EryPs, EryDs, and nRBCs. (I) Schematic diagram illustrating iron transport and mitochondrial heme biosynthesis pathways. (J-L) Expression of key genes involved in iron transportation (TFRC/Tfrc, SLC11A2/Slc11a2, and SLC25A37/Slc25a37) and heme biosynthesis (ALAS2/Alas2, HMBS/Hmbs, UROS/Uros, UROD/Urod, CPOX/Cpox, PPOX/Ppox, and FECH/Fech) in EryPs, EryDs, and nRBCs. The scRNA-seq analyses were based on 3 pregnancies per group for mouse tissues (3 embryos per pregnancy) and 4 lean vs 3 obese samples for human UCB. Statistical significance was determined using the Wilcoxon rank-sum test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.

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