PU.1 Functions in a Cell‐autonomous Manner to Control the Differentiation of Multipotential Lymphoid‐myeloid Progenitors
Open accessAbstract
Transcription factor PU.1 is required for the development of lymphoid and myeloid progenitors during fetal hematopoiesis. By generating chimeric animals using PU.1-/- ES cells or PU.1(-/-) hematopoietic progenitors, we demonstrate that PU.1 functions in an exclusively cell-autonomous manner to regulate the development of the lymphoid-myeloid system. Multipotential lymphoid-myeloid progenitors (AA4.1+, Lin-) are significantly reduced in PU.1(-/-) embryos and fail to differentiate into B lymphoid or myeloid cells in vitro. These results suggest that the lymphoid and myeloid lineages develop in the fetal liver from a common hematopoietic progenitor not shared with erythrocytes and megakaryocytes. Finally, the Ikaros gene is expressed in PU.1 mutant embryos, suggesting that PU.1 and Ikaros are independently required for specification of embryonic lymphoid cell fates.
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Microglial transcription factors are broadly expressed across myeloid lineages.
“these transcription factors are broadly expressed across myeloid lineages”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [76]
Systemic modulation of microglial transcription factors risks disrupting peripheral immunity.
“systemic modulation risks disrupting peripheral immunity”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [76]
Disruption of PU.1 eliminates or greatly inhibits T-cell development.
“Disruption of PU.1 has long been known to eliminate or greatly inhibit T-cell development, based on the dramatic phenotypes from the first lines of PU.1-knockout (Spi1 knockout) mice with unconditional, germline mutations (68–71).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [70]
PU.1 deficient mice do not develop myeloid cells.
“which confirms previous observations that PU.1 deficient mice do not develop myeloid cells19,20.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [19]
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- Authors
- Scott, E. W., Fisher, R. C., Olson, M. C., Kehrli, E. W., Simon, M. C., & Singh, H.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Singh, Harinder
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1997-04
- Volume
- 6
- Issue
- 4
- Pages
- 437-447
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2004092007
- Cited by
- 270
- References
- 6
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 10 · 2018: 3 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 11 · 2012: 6
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Korea Institute of Energy Research
- National Institutes of Health (5f32ai008933-02)
- Board of Research in Nuclear Sciences
- National Institute of Allergy and Infectious Diseases (F32 AI08933)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PU.1, Ikaros, hematopoietic lineage specification, fetal hematopoiesis, fetal liver, multipotent progenitors, B cell differentiation, myeloid differentiation, transcription factors, chimeric mice
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Bone Marrow Cells, Cell Count, Cell Differentiation, Cell Line, Chimera, DNA-Binding Proteins, Embryo, Mammalian, Erythropoiesis, Female, Gene Expression Regulation, Hematopoietic Stem Cells, Lymphoid Tissue, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Proto-Oncogene Proteins, Radiation Chimera, Transcription Factors, Trans-Activators, Erythrocyte Transfusion, Mice, Ikaros Transcription Factor
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