MRC National Institute for Medical Research, London
Science for Health
The adult pituitary gland contains stem/progenitor cells
21 February 2008
The pituitary gland adapts the proportion of each of its endocrine cell types to meet differing hormonal demands throughout life. There is circumstantial evidence that multipotent adult progenitor cells contribute to this plasticity, but these cells have not been identified.
Research teams at NIMR, led by Iain Robinson and Robin Lovell-Badge, have shown that a small population of progenitor cells in the adult pituitary gland express SOX2, a marker of several early embryonic progenitor and stem cell types, and form "pituispheres" in culture. These spheres can grow, form secondary spheres, and differentiate to all of the pituitary endocrine cell types, as well as folliculostellate cells. Differentiation of cells in the pituispheres was found to be associated with de novo the expression of nestin, SOX9, and S100. In vivo, cells expressing SOX2 are found throughout the embryonic pituitary and persist in the adult gland. However, unlike in the embryo, most of these SOX2+ cells also express SOX9 and S100. The researchers suggest that this SOX2+/SOX9+ population represents transit-amplifying cells, whereas the SOX2+/SOX9– cells we identify are multipotent progenitor/stem cells persisting in the adult pituitary.
The research was a collaboration between Iain Robinson, from NIMR's Division of Molecular Neuroendocrinology, Robin Lovell-Badge (pictured), from the Division of Stem Cell Biology & Developmental Genetics, and Mehul Dattani, from the UCL Institute of Child Health.
The existence of progenitor/stem cells in the pituitary remained an attractive but unproven hypothesis to explain some aspects of the physiological plasticity of the adult pituitary. We have now been able to show their existence and will pursue our work studying their properties and function in both physiological and pathological situations.
Dividing cell in a pituisphere
Phospho-histone H3 (green) and alpha-tubulin (red) immunostainings show the occurrence of cell division in SOX2 (blue) positive multipotent progenitors isolated from adult pituitary.
Progenitor cells in the adult pituitary gland
SOX2 (green) and E-cadherin (blue) are expressed in cells lining the pituitary cleft, whereas they are excluded from the differentiated cell population (Pit-1 positive, red).
3D view of a pituisphere
Pituitary progenitors express SOX2 (green). Cell boundary are visualized with phalloidin (red), and cell nuclei are stained with DAPI (blue).
Pituispheres contain progenitors
Pituispheres contain progenitors expressing SOX2 (green) and S100 protein (blue), able to differentiate into hormone-producing cells (green).
Original article
The research findings are published in full in:
Teddy Fauquier, Karine Rizzoti, Mehul Dattani, Robin Lovell-Badge, and Iain C. A. F. Robinson (2008)
SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland
Proceedings of the National Academy of Sciences, USA, epub ahead of print. Abstract
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