Language
English
Publication Date
4-1-2025
Journal
Experimental Hematology
DOI
10.1016/j.exphem.2025.104730
PMID
39900173
PMCID
PMC12261498
PubMedCentral® Posted Date
2-1-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the Klf4 gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and multilineage reconstitution, except for monocytes and T cells. However, the loss of KLF4 hindered hematologic reconstitution in competitive serial bone marrow transplants, highlighting a critical role for KLF4 in stress-induced hematopoiesis. Transcriptome analysis revealed an upregulation of NFκB2 and toll-like receptors (e.g., TLR4) in Klf4-null HSCs during homeostasis. Flow cytometry and immunoblot analysis confirmed the increased cell surface expression of TLR4 and the activation of NFκB2 in HSCs under homeostatic conditions, whereas NFκB2 expression drops after radiation compared with steady-state levels. Our findings suggest that the constitutive activation of the TLR4-NFκB2 pathway inhibits the ability of HSCs to regenerate blood after transplantation in cytoablated bone marrow.
Keywords
Kruppel-Like Factor 4, Animals, Kruppel-Like Transcription Factors, Hematopoiesis, Mice, Signal Transduction, Toll-Like Receptor 4, Hematopoietic Stem Cells, NF-kappa B, Mice, Knockout, Bone Marrow Transplantation, Hematopoietic Stem Cell Transplantation, Mice, Inbred C57BL, hematopoietic stem cells, self-renewal, bone marrow, KLF4
Published Open-Access
yes
Recommended Citation
Park, Chun Shik; Bridges, Cory S; Lewis, Andrew H; et al., "KLF4 Enhances Transplantation-Induced Hematopoiesis by Inhibiting TLRs and Noncanonical NFκB Signaling at a Steady State" (2025). Faculty, Staff and Students Publications. 6520.
https://digitalcommons.library.tmc.edu/baylor_docs/6520
Graphical Abstract