Concise Review: Balancing Stem Cell Self-Renewal and Differentiation with PLZF

Abstract

In recent years, the highly conserved promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16, ZNF145) has attracted attention as a multifunctional transcription factor involved in major biological processes during development. As a transcription factor, PLZF shows tight regulation in its cell-type-specific and stage-specific expression patterns. Emerging evidence shows that PLZF regulates the balance of self-renewal and differentiation in stem cells. However, the gene regulatory network of PLZF is only beginning to be understood. In this review, we discuss the diverse functions of PLZF, in particular its role in self-renewal versus differentiation of stem cells. We also discuss the current state of knowledge on the gene regulatory network of PLZF, in conjunction with its upstream factors, post-translational modifications and binding cofactors for multiprotein complexes. This review aims to provide the reader with an in-depth understanding of the molecular mechanisms underlying PLZF and the potential applications in tissue regeneration. STEM CELLS 2016;34:277-287 SIGNIFICANCE STATEMENTSIGNIFICANCE STATEMENT Stem cells posses the unique ability to maintain multipotency and selfrenew. Stem cell fate decisions, to self-renew or differentiate, is a key step in the therapeutic use of stem cells for regenerative medicine. In recent years, the highly conserved promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16, ZNF145) has attracted attention as a multifunctional transcription factor involved in stem cell biology. PLZF is expressed in long-term HSCs (LT-HSCs), spermatogonial stem cells and neural progenitors to maintain their selfrenewal. Interestingly, PLZF is also expressed during myeloid differentiation, na€ ıve T cells differentiating into effector T cells, and osteochondral differentiation of MSCs into bone and cartilage. Our labs have substantial experience with the effects of PLZF on the osteochondral differentiation of MSCs, and we would like to propose a model for how PLZF might balance stem cell self-renewal and differentiation as a transcription factor.

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability

“…For instance, downregulation of ZBTB16 would promote inflammation and proliferation of autoreactive T cells [21]. In contrast to the reduced ZFP36 expected to promote satellite cell activation, the increased CITED2 would be expected to reduce satellite cell activation [22, 23].…”

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

“…Overexpression of MUC1 in clinically tumor free tissue thus could play a dual role in cancer development. ZBTB16, zinc finger and BTB domain containing 16 (also known as PLZF or ZNF145), is a transcription factor involved in balancing stem cell self-renewal and differentiation and is tightly regulated in cell-type and developmental stage-specific manners [28]. Reactivation of factors involved in development is often seen in tumors, accordingly this factor could also have a dual tumor stimulatory role through stem cell renewal and/or inhibition of apoptosis.…”

Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced Leukemogenesis

“…Previous studies (5,7) showed that PLZF is strongly expressed in hematopoietic stem cells (HSCs) and immature progenitors. While Plzf is essential for self-renewal in spermatogenesis, it is not indispensable for normal hematopoiesis (8), but is involved in control of HSC homeostasis (9). In malignant hematopoiesis, we found that Plzf is critically involved in the aberrant self-renewal program induced by mixed lineage leukemia (MLL) fusion oncogenes (10).…”