Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

Stem Cells Translational Medicine
Chun S ParkDaniel Lacorazza

Abstract

Pluripotent and tissue-specific stem cells, such as blood-forming stem cells, are maintained through a balance of quiescence, self-renewal, and differentiation. Self-renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self-renewal, perhaps the most well-known factors are members of the Krüppel-like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF4 regulates gene expression through transcriptional activation or repression via either DNA binding or protein-to-protein interactions, the outcome of KLF4-mediated regulation largely depends on the cellular context, cell cycle regulation, chromatin structure, and the presence of oncogenic drivers. This study first summarizes the current understanding of the regulation of self-renewal by KLF proteins in embryonic stem cells through a KLF circuitry and then delves into the potential function of KLF4 in normal hematopoietic stem cells and its emerging role in leukemia-initiating cells from pediatric patients with T-cell acute lymphoblastic l...Continue Reading

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Citations

Jun 11, 2019·Stem Cells Translational Medicine·Stuart P Atkinson
Jul 8, 2020·Cells·Luis SousaMargarida D Amaral
Jan 12, 2020·BioFactors·Xiaoyan ChenHeng Zhang
Jan 12, 2021·Molecular Therapy. Nucleic Acids·Xiaoxue JiangDongdong Lu
Oct 17, 2020·OncoTargets and Therapy·Zhonglin Cai, Hongjun Li
Mar 5, 2021·PLoS Biology·Shirly Becker-HermanIdit Shachar
Mar 5, 2021·Oncotarget·Andrew Henry LewisH Daniel Lacorazza
May 8, 2021·European Journal of Pharmacology·Zohreh YaghobiBehzad Baradaran

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Methods Mentioned

BETA
immunoprecipitation
xenograft

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