Figure 7. HO‐1^+/+ expression in the recipients restores function and transcriptional profile of HO‐1^−/− LT‐HSCs.

• A
  Scheme of the experiment verifying if the HO‐1^+/+ niche is able to reverse phenotype of HO‐1^−/− LT‐HSCs.
• B
  Transplantation of HO‐1^−/− HSCs provides lower chimerism among HSPC fractions in primary recipients. Data are shown as mean ± SEM, n = 7–8 mice/group.
• C, D
  Transplantation of the same number of donor‐derived BM cells from primary recipients provides the same (C) PB chimerism and (D) BM LT‐HSC chimerism. Data are shown as mean ± SEM, n = 7–8 mice/group.
• E
  Analysis pipeline used to determine whether transplantation of HO‐1^−/− HSCs to the HO‐1^+/+ recipients reverses their transcriptional alterations.
• F
  Overlap between DEGs in young HO‐1^−/− HSCs and DEGs changed by transplantation alone. A total of 145 overlapping genes were excluded from further analysis.
• G
  GSEA based on 145 excluded genes indicates processes that cannot be analyzed with the pipeline.
• H
  Only 1 out of 267 DEGs identified in non‐transplanted HO‐1^−/− LT‐HSCs was still dysregulated in HO‐1^−/− LT‐HSCs transplanted twice to the wild‐type HO‐1^+/+.
• I
  Comparison of gene log‐fold changes in non‐transplanted HO‐1^−/− LT‐HSCs and HO‐1^−/− LT‐HSCs transplanted twice to the wild‐type HO‐1^+/+ showed that transplantation of HO‐1^−/− LT‐HSCs twice to the wild‐type niche reverses their transcriptional alterations.
• J
  GSEA based on genes that were altered in non‐transplanted HO‐1^−/− LT‐HSCs, but were normalized by double transplantation to the wild‐type niche.