Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Increased Fanconi C expression contributes to the emergency granulopoiesis response
Liping Hu, … , Elizabeth Hjort, Elizabeth A. Eklund
Liping Hu, … , Elizabeth Hjort, Elizabeth A. Eklund
Published August 8, 2013
Citation Information: J Clin Invest. 2013;123(9):3952-3966. https://doi.org/10.1172/JCI69032.
View: Text | PDF
Research Article Hematology Article has an altmetric score of 10

Increased Fanconi C expression contributes to the emergency granulopoiesis response

  • Text
  • PDF
Abstract

Emergency granulopoiesis is a component of the innate immune response that is induced in response to infectious or inflammatory challenge. It is characterized by the rapid expansion and differentiation of granulocyte/monocyte progenitor (GMP) populations, which is due in part to a shortened S-phase of the cell cycle. We found that IRF8 (also known as ICSBP), an interferon regulatory transcription factor that activates phagocyte effector genes during the innate immune response, activates the gene encoding Fanconi C (Fancc) in murine myeloid progenitor cells. Moreover, IRF8-induced Fancc transcription was augmented by treatment with IL-1β, an essential cytokine for emergency granulopoiesis. The Fanconi pathway participates in repair of stalled or collapsed replication forks during DNA replication, leading us to hypothesize that the Fanconi pathway contributes to genomic stability during emergency granulopoiesis. In support of this hypothesis, Fancc–/– mice developed anemia and neutropenia during repeated, failed episodes of emergency granulopoiesis. Failed emergency granulopoiesis in Fancc–/– mice was associated with excess apoptosis of HSCs and progenitor cells in the bone marrow and impaired HSC function. These studies have implications for understanding the pathogenesis of bone marrow failure in Fanconi anemia and suggest possible therapeutic approaches.

Authors

Liping Hu, Weiqi Huang, Elizabeth Hjort, Elizabeth A. Eklund

×

Figure 7

Alum injection does not expand myeloid progenitors or differentiating granulocytes in Fancc–/– mice.

Options: View larger image (or click on image) Download as PowerPoint
Alum injection does not expand myeloid progenitors or differentiating gr...
(A) Alum increases total bone marrow cells in WT but not FANCC-deficient mice. WT, Fancc+/–, and Fancc–/– mice were injected with Alum or saline. Bone marrow was harvested 2 weeks later, and total bone marrow mononuclear cells were counted. Statistically significant differences with versus without Alum are indicated by *P < 0.01 or ***P < 0.01 and with versus without FANCC-knockout by **P < 0.01. (B) Alum decreases SCA1+ cells and increases CD34+ in WT, but not FANCC-deficient, mice. Bone marrow from the mice above was analyzed by flow cytometry for immature (SCA1+CD34–) or committed myeloid progenitors (SCA1–CD34+GR1–). Statistically significant differences with versus without Alum are indicated by *P < 0.01, **P < 0.01, or #P < 0.01 and with versus without FANCC-knockout by ***P < 0.01. (C) Alum increases differentiating granulocytes in the bone marrow of WT mice but not FANCC-deficient mice. The bone marrow above was analyzed for differentiating myeloid progenitors (CD34–GR1+). Statistically significant differences with versus without Alum are indicated by *P < 0.01 and with versus without FANCC-knockout by **P < 0.01. (D) Bone marrow from FANCC-deficient mice is abnormal. Sternal bone marrow from mice above was examined microscopically (original magnification, ×40). Areas of differentiating granulocytes in WT bone marrow after Alum are encircled. A dysplastic megakaryocyte in control Fancc–/– bone marrow is indicated by an arrow, and hypersegmented granulocytes are indicated by asterisks. Hyaline debris in Fancc–/– bone marrow from Alum-treated mice is indicated by an arrow, areas of degrading cells are encircled, and abnormal granulocyte progenitors are indicated by asterisks.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
30 readers on Mendeley
See more details