Faculty Opinions recommendation of Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential.

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent central nervous system have been limited by methodological challenges resulting in only partial and transient OPC depletion. We have developed a novel pharmacogenetic model of conditional OPC ablation, resulting in the elimination of 99.7% of all OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting of OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRα-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRα+/NG2+ cells with the capacity to migrate and proliferate extensively throughout the dorsal anterior forebrain. Further application of this novel approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease.

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Abstract 860: Phenotypic Characterization Of Murine And Human Cardiac-resident Progenitor Cells Isolated On Basis Of Aldehyde-dehydrogenase Activity

Circulation ◽

10.1161/circ.116.suppl_16.ii_167-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Albert Spicher ◽

Andrea Meinhardt ◽

Marc-Estienne Roehrich ◽

Giuseppe Vassalli

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Progenitor Cells ◽

Aldehyde Dehydrogenase ◽

Adult Mouse ◽

Heart Cells ◽

Stem Cell Markers ◽

Aldh Activity ◽

Differentiation Potential ◽

Cellular Property

Identification of stem cells based on hematopoietic stem cell (HSC) surface markers, such as stem cell antigen-1 (Sca-1) and the c-kit receptor, has limited specificity. High aldehyde-dehydrogenase (ALDH) activity is a general cellular property of stem cells shared by HSC, neural, and intestinal stem cells. The presence of cells with high ALDH activity in the adult heart has not been investigated. Methods: Cells were isolated from adult mouse hearts, and from atrial appendage samples from humans with ischemic or valvular heart disease. Myocyte-depleted mouse Sca-1+, and lineage (Lin)-negative/c-kit+ human heart cells were purified with immunomagnetic beads. ALDH-high cells were identified using a specific fluorescent substrate, and sorted by FACS. Cell surface marker analysis was performed by flow cytometry. Results: Myocyte-depleted mouse heart cells contained 4.8+/−3.2% ALDH-high/SSC-low and 32.6+/−1.6% Sca-1+ cells. ALDH-high cells were Lin-negative, Sca-1+ CD34+ CD105+ CD106+, contained small CD44+ (27%) and CD45+ (15%) subpopulations, and were essentially negative for c-kit (2%), CD29, CD31, CD133 and Flk-1. After several passages in culture, ~20% of ALDH-high cells remained ALDH-high. Myocyte-depleted human atrial cells contained variable numbers of ALDH-high cells ranging from 0.5% to 11%, and 4% Lin-negative/c-kit+ cells. ALDH-high cells were CD29+ CD105+, contained a small c-kit+ subpopulation (5%), and were negative for CD31, CD45 and CD133. After 5 passages in culture, the majority of ALDH-high cells remained ALDH-high. Conclusions: Adult mouse and human hearts contain significant numbers of cells with high ALDH activity, a general cellular property that stem cells possess in different organs, and express stem cell markers (Sca-1 and CD34 in the mouse). The immunophenotype of cardiac-resident ALDH-high cells differs from that previously described for bone marrow ALDH-high HSC, and suggests that this cell population may be enriched in mesenchymal progenitors. Analysis of lineage differentiation potential of ALDH-high cells is in progress. ALDH activity provides a new, practical approach to purifying cardiac-resident progenitor cells.

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Abstract 2611: Cisplatin negatively affects CNS progenitor cells and behavior in the adult mouse

10.1158/1538-7445.am10-2611 ◽

2010 ◽

Author(s):

Nunes T. Ana ◽

Ruolan Han ◽

Kelcie Sprentall ◽

Ornella Santoni ◽

Mark Noble

Keyword(s):

Progenitor Cells ◽

Adult Mouse ◽

And Behavior

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Clonal Culture of Adult Mouse Lung Epithelial Stem/Progenitor Cells

Methods in Molecular Biology - Stem Cell Protocols ◽

10.1007/978-1-4939-1785-3_17 ◽

2014 ◽

pp. 231-241 ◽

Cited By ~ 7

Author(s):

Jonathan L. McQualter ◽

Ivan Bertoncello

Keyword(s):

Progenitor Cells ◽

Adult Mouse ◽

Mouse Lung ◽

Clonal Culture ◽

Lung Epithelial

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Reporter Expression, Induced by a Growth Hormone Promoter-Driven Cre Recombinase (rGHp-Cre) Transgene, Questions the Developmental Relationship between Somatotropes and Lactotropes in the Adult Mouse Pituitary Gland

Endocrinology ◽

10.1210/en.2006-1542 ◽

2007 ◽

Vol 148 (5) ◽

pp. 1946-1953 ◽

Cited By ~ 52

Author(s):

Raul M. Luque ◽

Geraldine Amargo ◽

Shinya Ishii ◽

Corrinne Lobe ◽

Roberta Franks ◽

...

Keyword(s):

Pituitary Gland ◽

Transgenic Mouse ◽

Anterior Pituitary ◽

Adult Mouse ◽

Small Subset ◽

Parental Line ◽

Pituitary Cells ◽

Placental Alkaline Phosphatase ◽

Developmental Studies ◽

Mouse Pituitary

This report describes the development and validation of the rGHp-Cre transgenic mouse that allows for selective Cre-mediated recombination of loxP-modified alleles in the GH-producing cells of the anterior pituitary. Initial screening of the rGHp-Cre parental line showed Cre mRNA was specifically expressed in the anterior pituitary gland of adult Cre+/− mice and cephalic extracts of e17 Cre+/− fetuses. Heterozygote rGHp-Cre transgenic mice were crossbred with Z/AP reporter mice to generate Cre+/−,Z/AP+/− offspring. In this model system, the GH promoter-driven, Cre-mediated recombination of the Z/AP reporter leads to human placental alkaline phosphatase (hPLAP) expression that serves to mark cells that currently produce GH, in addition to cells that would have differentiated from GH cells but currently do not express the GH gene. Double immunocytochemistry of adult male and female Cre+/−,Z/AP+/− pituitary cells revealed the majority (∼99%) of GH-producing cells of the anterior pituitary also expressed hPLAP, whereas ACTH-, TSH-, and LH-producing cells were negative for hPLAP, confirming previous reports that corticotropes, thyrotropes, and gonadotropes develop independently of the somatotrope lineage. A small subset (∼10%) of the prolactin-producing cells was positive for hPLAP, consistent with previous reports showing lactotropes can arise from somatotropes during pituitary development. However, the fact that 90% of prolactin-producing cells were negative for hPLAP suggests that the majority of lactotropes in the adult mouse pituitary gland develop independently of the somatotrope lineage. In addition to developmental studies, the rGHp-Cre transgenic mouse will provide a versatile tool to study the role of a variety of genes in somatotrope function and neoplastic transformation.

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