Tfe3 expression is closely associated to macrophage terminal differentiation of human hematopoietic myeloid precursors.
The MItf-Tfe family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors encodes four family members: MItf, Tfe3, TfeB and TfeC. In vitro, each protein of the family binds DNA in a homo- or heterodimeric form with other family members. Tfe3 is involved in chromosomal translocations recurrent in different tumors and it has been demonstrated, by in vivo studies, that it plays, redundantly with MItf, an important role in the process of osteoclast formation, in particular during the transition from mono-nucleated to multi-nucleated osteoclasts. Since mono-nucleated osteoclasts derive from macrophages we investigated whether Tfe3 might play a role upstream during hematopoietic differentiation. Here we show that Tfe3 is able to induce mono-macrophagic differentiation of U937 cells, in association with a decrease of cell proliferation and an increase of apoptosis. We also show that Tfe3 does not act physiologically during commitment of CD34+ hematopoietic stem cells (HSCs), since it is not able to direct HSCs toward a specific lineage as observed by clonogenic assay, but is a strong actor of terminal differentiation since it allows human primary myeloblasts' maturation toward the macrophage lineage.
Zanocco-Marani
Tommaso
T
Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Via Campi 287, 41100, Modena, Italy.
Vignudelli
Tatiana
T
Gemelli
Claudia
C
Pirondi
Sara
S
Testa
Anna
A
Montanari
Monica
M
Parenti
Sandra
S
Tenedini
Elena
E
Grande
Alexis
A
Ferrari
Sergio
S
D000943:Antigens, Differentiation / Q000032:analysis; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005312:Fetal Blood / Q000378:metabolism / Q000502:physiology; D020868:Gene Silencing; D042381:Granulocyte Precursor Cells / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000493:pharmacokinetics / Q000494:pharmacology; D014161:Transduction, Genetic
D000943:Antigens, Differentiation; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018950:Lipopolysaccharide Receptors; C069203:TFE3 protein, human; D013755:Tetradecanoylphorbol Acetate