A Postnatal Pax7 Progenitor Gives Rise to Pituitary Adenomas.
Pituitary adenomas are classified into functioning and nonfunctioning (silent) tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis and the cell of origin for pituitary adenoma subtypes remain to be elucidated. Employing a tamoxifen-inducible mouse model, we demonstrate that a novel postnatal Pax7(+) progenitor cell population in the pituitary gland gives rise to silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is conditionally deleted. While Pax transcriptional factors are critical for embryonic patterning as well as postnatal stem cell renewal for many organs, we have discovered that Pax7 marks a restricted cell population in the postnatal pituitary intermediate lobe. This Pax7(+) early progenitor cell population is overlapping but ontologically downstream of the Nestin(+) pituitary stem cell population, yet upstream of another newly discovered Myf6(+) late progenitor cell population. Interestingly, the Pax7(+) progenitor cell population is evolutionarily conserved in primates and humans, and Pax7 expression is maintained not only in murine tumors but also in human functioning and silent corticotropinomas. Taken together, our results strongly suggest that human silent corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate lobe, a region of the human pituitary bearing closer scientific interest as a reservoir of pituitary progenitor cells.
Hosoyama
Tohru
T
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA.
Nishijo
Koichi
K
Garcia
Melinda M
MM
Schaffer
Beverly S
BS
Ohshima-Hosoyama
Sachiko
S
Prajapati
Suresh I
SI
Davis
Michael D
MD
Grant
Wilmon F
WF
Scheithauer
Bernd W
BW
Marks
Daniel L
DL
Rubin
Brian P
BP
Keller
Charles
C
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