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Cited by 44Hematopoietic Stem Cell TransplantationT-cell and B-cell ImmunologyDevelopmental Biology and Gene Regulation

Early T-cell progenitors are the major granulocyte precursors in the adult mouse thymus

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De Obaldia, Maria Elena, Bell, J. Jeremiah, Bhandoola, Avinash·2013·Blood
DOI 10.1182/blood-2012-08-451773PMC PMC3538332
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Abstract

The mouse thymus supports T-cell development, but also contains non–T-cell lineages such as dendritic cells, macrophages, and granulocytes that are necessary for T-cell repertoire selection and apoptotic thymocyte clearance. Early thymic progenitors (ETPs) are not committed to the T-cell lineage, as demonstrated by both in vitro and in vivo assays. Whether ETPs realize non–T-cell lineage potentials in vivo is not well understood and indeed is controversial. In the present study, we investigated whether ETPs are the major precursors of any non–T-lineage cells in the thymus. We analyzed the development of these populations under experimental circumstances in which ETPs are nearly absent due to either abrogated thymic settling or inhibition of early thymic development by genetic ablation of IL-7 receptorα or Hes1. Results obtained using multiple in vivo approaches indicate that the majority of thymic granulocytes derive from ETPs. These data indicate that myelolymphoid progenitors settle the thymus and thus clarify the pathways by which stem cells give rise to downstream blood cell lineages.

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  • In mouse, natural loss of access to dendritic cell and granulocyte programs agrees with the timing of PU.1 downregulation.

    “there is good agreement between the cells' natural loss of access to the dendritic cell and granulocyte programs, on the one hand, and the timing of PU.1 downregulation, on the other hand (33, 39–42).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [42]

    The Introduction (page unavailable) says mouse early T-cell progenitors gradually lose non-T-cell potentials, including dendritic-cell and myeloid potential, as they progress toward T-cell commitment. The Results (page unavailable) report that committed DN3 cells did not generate thymic granulocytes. Our copy does not establish the claimed agreement with the timing of PU.1 downregulation; searches for PU.1 and downregulation found no passage addressing it. (LLM, conf=0.85)

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Authors
De Obaldia, M. E., Bell, J. J., & Bhandoola, A.
Affiliations
  • Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
  • University of Pennsylvania (US)
ORCID
Bhandoola, Avinash
Venue
Blood
Publisher
American Society of Hematology
Published
2013-01-03
Volume
121
Issue
1
Pages
64-71
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2012-08-451773
PMC
PMC3538332
OpenAlex
W2010422802
Cited by
44
References
4
Citations by year
2025: 1 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 5
FWCI
2.77
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL110741)
  • National Cancer Institute (T32CA009140, T32 CA 09140, P30CA016520)
  • National Institute of General Medical Sciences (T32GM007229, T32GM07229)
  • National Institute of Allergy and Infectious Diseases (F32AI080091, 1-F32-AI-080091-01A1, R01AI059621)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
myeloid lineage commitment, IL-7 receptor alpha, Hes1, thymus, hematopoietic stem cell differentiation, dendritic cells, macrophages
MeSH terms
Transcription Factor HES-1, Animals, Cell Movement, Female, Granulocytes, Hematopoietic Stem Cells, Mice, Inbred C57BL, Mice, Transgenic, Radiation Chimera, Thymus Gland, Bone Marrow Transplantation, T-Lymphocyte Subsets, Genes, Reporter, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Cell Lineage, Animals, Congenic, Receptors, Interleukin-7, Lymphopoiesis, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins

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