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Infection perturbs Bach2- and Bach1-dependent erythroid lineage ‘choice’ to cause anemia
Abstract
Elucidation of how the differentiation of hematopoietic stem and progenitor cells (HSPCs) is reconfigured in response to the environment is critical for understanding the biology and disorder of hematopoiesis. Here we found that the transcription factors (TFs) Bach2 and Bach1 promoted erythropoiesis by regulating heme metabolism in committed erythroid cells to sustain erythroblast maturation and by reinforcing erythroid commitment at the erythro-myeloid bifurcation step. Bach TFs repressed expression of the gene encoding the transcription factor C/EBPβ, as well as that of its target genes encoding molecules important for myelopoiesis and inflammation; they achieved the latter by binding to their regulatory regions also bound by C/EBPβ. Lipopolysaccharide diminished the expression of Bach TFs in progenitor cells and promoted myeloid differentiation. Overexpression of Bach2 in HSPCs promoted erythroid development and inhibited myelopoiesis. Knockdown of BACH1 or BACH2 in human CD34 + HSPCs impaired erythroid differentiation in vitro. Thus, Bach TFs accelerate erythroid commitment by suppressing the myeloid program at steady state. Anemia of inflammation and myelodysplastic syndrome might involve reduced activity of Bach TFs.
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“The heme-dependent transcriptional repressor BACH-1 plays an essential role in the heme induced increase of myeloid cells, since it was shown that heme binding to BACH-1 causes a shift from erythropoiesis towards myelopoiesis in the bone marrow 52 , similar to observed in this study.”
From Heme induces innate immune memory (2019) · cites this paper as [52]
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Self-citationC/EBPβ is required for 'emergency' granulopoiesis
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Cited by
Sorted by citations
Jang (2019) · doi:10.1038/s12276-019-0352-x · Cited by 114
Heme induces innate immune memory
Jentho, E., Novakovic, B., Ruiz-Moreno, C., Kourtzelis, I., Martins, R., Chavakis, T., Soares, M. P., Kalafati, L., Guerra, J., Roestel, F., et al. (2019) · doi:10.1101/2019.12.12.874578 · Cited by 10
Metadata
- Authors
- Kato, H., Itoh-Nakadai, A., Matsumoto, M., Ishii, Y., Watanabe-Matsui, M., Ikeda, M., Ebina-Shibuya, R., Sato, Y., Kobayashi, M., Nishizawa, H., Suzuki, K., Muto, A., Fujiwara, T., Nannya, Y., Malcovati, L., Cazzola, M., Ogawa, S., Harigae, H., & Igarashi, K.
- Venue
- Nature Immunology
- Published
- 2018-09-24
- Volume
- 19
- Issue
- 10
- Pages
- 1059-1070
- ISSN
- 1529-2908
- 1529-2916
- Cited by
- 44
- References
- 8
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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- Kato, H., Itoh-Nakadai, A., Matsumoto, M., Ishii, Y., Watanabe-Matsui, M., Ikeda, M., Ebina-Shibuya, R., Sato, Y., Kobayashi, M., Nishizawa, H., Suzuki, K., Muto, A., Fujiwara, T., Nannya, Y., Malcovati, L., Cazzola, M., Ogawa, S., Harigae, H., & Igarashi, K. (2018). Infection perturbs Bach2- and Bach1-dependent erythroid lineage ‘choice’ to cause anemia. Nature Immunology. https://doi.org/10.1038/s41590-018-0202-3