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. 2022;38(3):219-226.
doi: 10.5146/tjpath.2021.01564.

Analysis of DUX4 Expression in Bone Marrow and Re-Discussion of DUX4 Function in the Health and Disease

Ceren Hangul  1 , Oznur Tokta, Sibel Berker Karauzum, Bahar Akkaya, Hulya Yildirim, Funda Tayfun Kupesiz, Ayse Nur Akinel
Affiliations

Analysis of DUX4 Expression in Bone Marrow and Re-Discussion of DUX4 Function in the Health and Disease

Ceren Hangul et al. Turk Patoloji Derg. 2022.

Abstract

Objective: DUX4 is an embryonic transcription factor (TF) later silenced in somatic tissues, while active in germline testis cells. Re-expression in somatic cells has been revealed to be present in pathologic conditions such as dystrophy, leukemia, and other cancer types. Embryonic cells, cancer cells and testis cells that show DUX4 expression are pluri-multipotent cells. This lead us to question "Could DUX4 be a TF that is active in certain types of potent somatic cells?" As a perfect reflection of the potent cell pool, we aimed to reveal DUX4 expression in the bone marrow.

Material and method: Bone marrow aspiration materials of seven healthy donors aged between 3 and 32 (2 males/5 females) were investigated with qPCR analysis after RNA isolation for the presence of DUX4 full length mRNA expression. Samples have been investigated for protein existence of DUX4 via immunohistochemistry in two donors that had sufficient aspiration material.

Results: DUX4 mRNA expression was present in all donors, with higher expression compared to B-actin. DUX4 positive stained cells were also detected by immunohistochemistry.

Conclusion: With these results, novel expression for DUX4 in hematopoietic tissue is described. Further studies on the function of DUX4 in hematopoietic cells can shed light on DUX4-related pathways, and contribute to the treatment of DUX4-related diseases such as B-ALL, other cancers, and facioscapulohumeral muscular dystrophy.

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
A) qPCR analysis of seven healthy donors with different ages and gender. Blue bars represent DUX4 mRNA expression and grey bars represent housekeeping B-actin mRNA expression. B) DeltaCT values of DUX-fl mRNA expression in bone marrow aspirates.
Figure 2
Figure 2
DUX4 Immunohistochemistry figures of bone marrow aspirates of Donor 2. A) Red arrows indicate brown cells that are positive for DUX4 protein, blue arrows indicate DUX4 negative cells. B) Red arrows indicate DUX4 positive cells, blue arrows indicate DUX4 negative cells, black arrow indicates DUX4 positive cell with its huge nucleus. All photographs have been taken 20X microscopic magnification.
Figure 3
Figure 3
DUX4 Immunohistochemistry figures of bone marrow aspirates of Donor 3. A) Red arrows indicate brown cells that are positive for DUX4 protein, blue arrows indicate DUX4 negative cells. B) Black arrow indicates DUX4 positive huge cell with an empty cytoplasmic area around, indicating a megakaryocyte. All photographs have been taken 20X microscopic magnification.
*Asterisks indicate additional hypothesis that is suggested for the role of DUX4. DUX4-fl; full length, DUX4r; DUX4 re-arrangement/fusion.
Figure 4
Schematic presentation for the DUX4 role in (A) healthy hematopoietic cells, healthy embryonic cells, healthy skeletal differentiation and FSHD; (B) in malignancy. Revealed knowledge referred with authors.
See this image and copyright information in PMC

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