Runx1 is involved in primitive erythropoiesis in the mouse
Open accessAbstract
Targeted disruption of the Runx1/ AML1 gene in mice has demonstrated that it is required for the emergence of definitive hematopoietic cells but that it is not essential for the formation of primitive erythrocytes. These findings led to the conclusion that Runx1 is a stage-specific transcription factor acting only during definitive hematopoiesis. However, the zebrafish and Xenopus homologs of Runx1 have been shown to play roles in primitive hematopoiesis, suggesting that mouse Runx1 might also be involved in the development of primitive lineages. In this study, we show that primitive erythrocytes in Runx1(-/-) mice display abnormal morphology and reduced expression of Ter119, Erythroid Kruppel-like factor (EKLF, KLF1), and GATA-1. These results suggest that mouse Runx1 plays a role in the development of both primitive and definitive hematopoietic cells.
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Emergence of hematopoietic progenitors from the hemangioblast coincides with the activation of transcription factors required for hematopoiesis, such as Runx1 and Gata1.
“Emergence of hematopoietic progenitors from the hemangioblast coincides with the activation of transcription factors required for hematopoiesis, such as Runx1 and Gata1”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Yokomizo et al., 2008
The Results section ('Reduced expression of EKLF and GATA-1 in Runx1 -/ embryos'; page not provided) identifies GATA-1 as important for erythrocyte differentiation and reports reduced GATA-1 expression in Runx1-deficient cells. 'Transgenic rescue of Runx1 -/ primitive erythrocytes' says GATA-1 is expressed in early erythroid progenitors. The paper does not establish that activation of both factors coincides with progenitors emerging from the hemangioblast. (LLM, conf=0.82)
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References 41 · Cited by 78
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- [1]1. Dzierzak E. Hematopoietic stem cells and their precursors: developmental diversity and lineage relationships. Immunol Rev. 2002;187:126-138
- [2]2. Ciau-Uitz A, Walmsley M, Patient R. Distinct origins of adult and embryonic blood in Xenopus. Cell. 2000;102:787-796
- [4]4. Palis J, Yoder MC. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp Hematol. 2001;29:927-936
- [5]5. Ema M, Yokomizo T, Wakamatsu A, Terunuma T, Yamamoto M, Takahashi S. Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin, and CD34 in the mouse embryo. Blood. 2006;108:4018-4024
- [6]6. McGrath KE, Koniski AD, Malik J, Palis J. Circulation is established in a stepwise pattern in the mammalian embryo. Blood. 2003;101:1669-1676
- [8]8. Speck NA, Gilliland DG. Core-binding factors in haematopoiesis and leukaemia. Nature Reviews Cancer. 2002;2:502-513
- [9]9. Yoshikawa M, Senzaki K, Yokomizo T, Takahashi S, Ozaki S, Shiga T. Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons. Dev. Biol. 2007;303:663-674
- [10]10. Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996;84:321-330
- [11]11. Wang Q, Stacy T, Binder M, et al. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc. Natl. Acad. Sci. USA. 1996;93:3444-3449
- [12]12. Okada H, Watanabe T, Niki M, et al. AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene. 1998;17:2287-2293
- [15]15. Kalev-Zylinska ML, Horsfield JA, Flores MV, et al. Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis. Development. 2002;129:2015-2030
- [16]16. Burns CE, Traver D, Mayhall E, Shepard JL, Zon LI. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev. 2005;19:2331-2342
- [17]17. Tracey WD Jr, Pepling ME, Horb ME, Thomsen GH, Gergen JP. A Xenopus homologue of aml-1 reveals unexpected patterning mechanisms leading to the formation of embryonic blood. Development. 1998;125:1371-1380
- [18]18. Lacaud G, Gore L, Kennedy M, et al. Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro. Blood. 2002;100:458-466
- [19]19. Onodera K, Takahashi S, Nishimura S, et al. GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis. Proc Natl Acad Sci USA. 1997;94:4487-4492
- [20]20. Yokomizo T, Takahashi S, Mochizuki N, et al. Characterization of GATA-1 + hemangioblastic cells in the mouse embryo. EMBO J. 2007;26:184-196
- [21]21. Palis J, Robertson S, Kennedy M, Wall C, Keller G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development. 1999;126:5073-5084
- [22]22. Suzuki N, Suwabe N, Ohneda O, et al. Identification and characterization of 2 types of erythroid progenitors that express GATA-1 at distinct levels. Blood. 2003;102:3575-83
- [23]23. Suzuki Y, Nakayama M. Differential profiles of gene expressed in neonatal brain of 129X1/SvJ and C57BL/6J mice: a database to aid in analyzing DNA microarrays using nonisogenic gene-targeted mice. DNA Research. 2003;10:263-275
- [24]24. Drissen R, von Lindern M, Kolbus A, et al. The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability. Mol. Cell. Biol. 2005;25:5205-5214
- [25]25. Hodge D, Coghill E, Keys J, et al. A global role for EKLF in definitive and primitive erythropoiesis. Blood. 2006;107:3359-3370
- [26]26. Kihm AJ, Kong Y, Hong W, et al. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature 2002;417:758-763
- [27]27. Anderson KP, Crable SC, Lingrel JB. Multiple proteins binding to a GATA-E box-GATA motif regulate the erythroid Kruppel-like factor (EKLF) gene. J. Biol. Chem. 1998;273:14347-14354
- [28]28. Suwabe N, Takahashi S, Nakano T, Yamamoto M. GATA-1 regulates growth and differentiation of definitive erythroid lineage cells during in vitro ES cell differentiation. Blood. 1998;92:4108-4118
- [29]29. Ferreira R, Ohneda K, Yamamoto M, Philipsen S. GATA1 Function, a Paradigm for Transcription Factors in Hematopoiesis. Mol Cell Biol. 2005;25:1215-1227
- [30]30. Castilla LH, Wijmenga C, Wang Q, et al. Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell. 1996;87:687-696
- [31]31. Huang G, Shigesada K, Wee HJ, Liu PP, Osato M, Ito Y. Molecular basis for a dominant inactivation of RUNX1/AML1 by the leukemogenic inversion 16 chimera. Blood. 2004;103:3200-3207
- [32]32. Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH. Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc. Natl. Acad. Sci. U S A. 1996;93:12355-12358
- [33]33. Nakajima O, Takahashi S, Harigae H, et al. Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J. 1999;18:6282-6289
- [34]34. Elagib KE, Racke FK, Mogass M, Khetawat R, Delehanty LL, Goldfarb AN. RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood. 2003;101:4333-4341
- [35]35. Fossett N, Hyman K, Gajewski K, Orkin SH, Schulz RA. Combinatorial interactions of serpent, lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis. Proc. Natl. Acad. Sci. U S A. 2003;100:11451-11456.
- [36]36. Gurbuxani S, Vyas P, Crispino JD. Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome. Blood. 2004;103:399-406
- [37]37. North TE, Stacy T, Matheny CJ, Speck NA, de Bruijn MF. Runx1 is expressed in adult mouse hematopoietic stem cells and differentiating myeloid and lymphoid cells, but not in maturing erythroid cells. Stem Cells. 2004;22:158-168
- [38]38. Yamasaki H, Era T, Asou N, et al. High degree of myeloid differentiation and granulocytosis is associated with t(8;21) smoldering leukemia. Leukemia. 1995;9:1147-1153.
- Authors
- Yokomizo, T., Hasegawa, K., Ishitobi, H., Osato, M., Ema, M., Ito, Y., Yamamoto, M., & Takahashi, S.
- Affiliations
- University of Tsukuba (JP)
- Institute of Molecular and Cell Biology (SG)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-04-15
- Volume
- 111
- Issue
- 8
- Pages
- 4075-4080
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1996300461
- Cited by
- 78
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 9 · 2012: 3
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (acceptedVersion)
- Terrestrial Environment Research Center (University of Tsukuba) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- RUNX1, primitive erythropoiesis, definitive hematopoiesis, erythrocyte morphology, Ter119, EKLF, KLF1, GATA-1, hematopoietic development
- MeSH terms
- Animals, Cell Differentiation, Embryo, Mammalian, Erythrocytes, Erythropoiesis, Mice, Inbred C57BL, Mice, Transgenic, RNA, Yolk Sac, Down-Regulation, Erythroid Precursor Cells, Oligonucleotide Array Sequence Analysis, Core Binding Factor Alpha 2 Subunit, GATA1 Transcription Factor, Mice, Kruppel-Like Transcription Factors
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