scholarly journals 268.Identifying markers for stromal stem/progenitor cells in human endometrium

2004 ◽  
Vol 16 (9) ◽  
pp. 268 ◽  
Author(s):  
K. E. Schwab ◽  
C. E. Gargett
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Endometrial Tissue ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
Endometrial Stromal Cell ◽  
Cell Markers

The endometrium is divided into upper functionalis, which rapidly grows then differentiates before being shed, and lower basalis, from which cyclical regeneration begins. A small proportion of endometrial stromal cells have been identified with clonogenic activity, a functional property of stem cells (1). We hypothesised that stromal stem/progenitor cells expressing known stem cell markers reside in the basalis. The aims of this study were to: (1) investigate the clonogenic activity of human endometrial stromal cell populations enriched and depleted for known stem cell markers, and (2) identify a marker that will differentiate basalis from functionalis stroma. Endometrial tissue acquired from 23 ovulating women undergoing hysterectomy was digested with collagenase to produce single cell suspensions. Leukocytes and epithelial cells were removed, and stromal cells analysed by flow cytometry, FACS sorted into enriched and depleted populations, and cultured for clonal analysis as described (1). Markers analysed included stem cell markers, STRO-1, CD133, CD45 and CD34, and an endometrial stromal cell marker, CD90 (2). Immunohistochemical analysis of CD90 was performed on full thickness human endometrial tissue. CD45– endometrial stromal cell populations contained 2.13 � 0.65% (n = 13) STRO-1+, and 5.43 � 1.42% (n = 16) CD133+ cells. Stromal cell populations enriched (0.65 � 0.42%) and depleted (0.95 � 0.58%) for STRO-1 showed no significant difference (P = 0.19, n = 5) for clonogenic activity. Surprisingly, clonogenicity of CD133+ stromal cells (0.74 � 0.56%) was lower than CD133– (3.89 � 1.35%) cells (P = 0.03, n = 6). Immunohistochemical staining showed strong CD90 staining in the functionalis, with lighter staining in the basalis. These observations were confirmed by flow cytometric analysis which identified two distinct populations (n = 9), CD90low (19.55 � 4.35%) and CD90hi (74.71 � 5.20%). Clonogenic analysis of these two populations is underway. Interestingly, dual-colour flow cytometry showed the CD133+ cells to be CD90low (n = 7). Further analysis suggests that the CD90lowCD133+ population are CD45–CD34+, suggesting endothelial progenitor cells. This study identified CD90 as a marker that distinguishes basalis and functionalis stroma, and demonstrated that STRO-1 and CD133 are not functional markers for clonogenic endometrial stromal stem/progenitor cells. (1) Chan RW, Schwab KE, Gargett CE (2004) Biol. Reprod. 70, in press. (2) Fernandez-Shaw S, Shorter SC, Naish CE, Barlow DH, Starkey PM (1992) Hum. Reprod. 7,156–161.

The expression of mesenchymal and embryonic stem cell markers by human limbal Stromal cells

2011 ◽  
Author(s):  
Moon Nian Lim ◽  
Umapathy Thiageswari ◽  
Othman Ainoon ◽  
P. J. N. Baharuddin ◽  
R. A. Jamal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Stromal Cells ◽  
Embryonic Stem ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Embryonic Stem Cell Markers

scholarly journals Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8377 ◽  
Author(s):  
Wendy W. Hwang-Verslues ◽  
Wen-Hung Kuo ◽  
Po-Hao Chang ◽  
Chi-Chun Pan ◽  
Hsing-Hui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Human Breast Cancer ◽  
Stem Cell Markers ◽  
Human Breast ◽  
Cell Markers

scholarly journals Molecular Characterization of c-Abl/c-Src Kinase Inhibitors Targeted against Murine Tumour Progenitor Cells that Express Stem Cell Markers

PLoS ONE ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. e14143 ◽  
Author(s):  
Thomas Kruewel ◽  
Silvia Schenone ◽  
Marco Radi ◽  
Giovanni Maga ◽  
Astrid Rohrbeck ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Molecular Characterization ◽  
Kinase Inhibitors ◽  
Src Kinase ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Murine Tumour

Identification of Novel Surface Markers and Targets In Neoplastic Stem Cells In AML and CML: a Flow-Gene-Flow Screen Approach.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1575-1575 ◽  
Author(s):  
Harald Herrmann ◽  
Sabine Cerny-Reiterer ◽  
Irina Sadovnik ◽  
Viviane Winter ◽  
Katharina Blatt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Gene Chip ◽  
Cytokine Receptors ◽  
Stem Cell Markers ◽  
Surface Markers ◽  
Leukemic Stem Cells

Abstract Abstract 1575 The concept of leukemic stem cells (LSC) is increasingly employed to explain the biology of various myeloid neoplasms and to screen for pivotal targets, with the hope to improve drug therapy through elimination of disease-initiating cells. Although the stem cell hypothesis may apply to all neoplasms, leukemia-initiating cells have so far only been characterized in some detail in myeloid leukemias. In an attempt to identify novel cell surface markers and targets on leukemic stem cells (LSC) in acute (AML) and chronic myeloid leukemia (CML), we examined CD34+/CD38- and CD34+/CD38+ populations of leukemic cells in a cohort of patients with AML (n=55) and CML (n=20). In a first step, cell surface antigen profiles were determined by multicolor flow cytometry. In this screen, we were able to show that CD34+/CD38- LSC in AML and CML consistently express certain cytokine receptors, including G-CSFR (CD114), SCFR/KIT (CD117), and IL-3RA (CD123). The low affinity IL-2R (CD25) was detectable on CD34+/CD38- stem cells in patients with CML, and in a subset of AML patients. Other cytokine receptors (R) such as FLT3, IGF-1R, endoglin (CD105), GM-CSFRA (CD116), and OSMR were expressed variably on CD34+/CD38- progenitor cells, whereas the EPOR was not detectable on LSC. We were also able to detect several established therapeutic targets on LSC, including CD33 and CD44. Whereas CD44 was consistently expressed on all LSC in all donors, CD33 was found to be expressed variably on subpopulations of LSC in AML and CML, depending on the phase and type of disease. By using cytokine ligands (G-CSF, IL-3, SCF, EPO) and targeted drugs, we were also able to confirm that identified cytokine receptors and targets were functionally active molecules and potentially relevant targets. In a next step, highly enriched (purity >98%) sorted CD34+/CD38- cells, CD34+/CD38+ cells, and CD34- cells were collected in patients with AML and CML, and in 3 cord blood samples as controls. Purified cells were subjected to gene chip analyses, qPCR, and functional analyses. The identity of leukemic progenitors was confirmed by FISH, and expression of markers and targets in CML stem cells and AML stem cells was confirmed by qPCR. In gene chip analyses, we screened for novel LSC markers and targets. Candidate genes were selected based and their specific expression in progenitor cell fractions and surface membrane location, which was confirmed by antibody staining experiments. Novel stem cell markers identified so far include ROBO4, NPDC-1, and CXCR7. The previously described surface markers MDR-1 and CLL-1 were also identified by flow cytometry, but were also found to be expressed on more mature hematopoietic cells. By contrast, ROBO4 was found to be expressed preferentially on CD34+/CD38- stem cells, but less abundantly on CD34+/CD38+ progenitor cells in CML. Interestingly, whereas ROBO4 was expressed on CD34+/CD38- stem cells in most patients with CML, ROBO4 expression on leukemic stem cells was only found in a subset of AML patients. By contrast, CD34+/CD38- stem cells in AML frequently expressed CLL-1 and NPDC-1 on their surface. In conclusion, we have identified novel markers and targets in CD34+/CD38- progenitor cells in AML and CML. These markers may be useful for the identification and isolation of leukemic stem cells in AML and CML, and for the validation of drug effects on these cells. Disclosures: De Angelis: Biopharm R&D, GSK: Employment. Holmes:Biopharm R&D, GSK: Employment. Valent:Domantis: Research Funding.

CD34+Corneal Stromal Cells Are Bone Marrow-Derived and Express Hemopoietic Stem Cell Markers

Stem Cells ◽  
2005 ◽  
Vol 23 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Magdaléna Sosnová ◽  
Monika Bradl ◽  
John V. Forrester
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stromal Cells ◽  
Hemopoietic Stem Cell ◽  
Stem Cell Markers ◽  
Cell Markers

scholarly journals Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Zongzhe Jiang ◽  
Jingjing Tian ◽  
Wenjian Zhang ◽  
Hao Yan ◽  
Liping Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Progenitor Cells ◽  
Nude Mice ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
In Vitro Induction

Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreatic β cell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19. Of note, FoxO1 knockdown or FoxO1 inhibitor significantly upregulated Ngn3 and insulin as well as the markers such as Glut2, Kir6.2, SUR1, and VDCC, which are designated for mature β cells. On the contrary, overexpression of FoxO1 suppressed the induction and reduced expression of these β cell markers. Taken together, these results suggest that FoxO1 may act as a repressor to inhibit cell differentiation in human fetal pancreatic progenitor cells.

003. ENDOMETRIUM: CINDERELLA TISSUE IN A STEM CELL WORLD

2009 ◽  
Vol 21 (9) ◽  
pp. 3
Author(s):  
C. E. Gargett
Keyword(s):  
Stem Cells ◽  
Endometrial Cancer ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Human Endometrium ◽  
Cancer Tissue ◽  
Stem Cell Markers ◽  
Epithelial Progenitor Cells

Despite human endometrium undergoing more than 400 cycles of regeneration, differentiation and shedding during a woman's reproductive years, and that in non-menstruating species (eg rodents) there are cycles of endometrial growth and apoptosis, endometrial stem/progenitor cells have only recently been identified. Since there are no specific stem cell markers, initial studies using functional approaches identified candidate epithelial and stromal endometrial stem/progenitor cells as colony forming cells/units (CFU) (1). Further evaluation of key stem cell properties of individual CFU demonstrated that rare EpCAM+ epithelial cells and EpCAM- stromal cells underwent self renewal by serial subcloning >3 times and underwent >30 population doublings in culture. Clonally-derived epithelial cells differentiated into cytokeratin+ gland-like structures. Single stromal cells were multipotent as they differentiated into 4 mesodermal lineages; myogenic, adipogenic, osteoblastic and chondrogenic, suggesting that human endometrium contains a rare population of epithelial progenitor cells and mesenchymal stem cells (MSC) (2). Transplantation of freshly isolated human endometrial cells into immunocompromised mice reconstructed endometrial tissue that responded to estrogen and progesterone (3). Endometrial MSC can be prospectively isolated by co-expression of CD146 and PDGFRβ (4), but not Stro-1, a bone marrow MSC marker (5). Currently there are no known markers of endometrial epithelial progenitor cells. Endometrial cancer tissue harbours a small subpopulation of clonogenic, self-renewing, tumour-initiating cells, producing tumours that recapitulate parent tumours in histoarchitecture and differentiation markers (ERα, PR, cytokeratin, vimentin) when xenografted into mice, suggesting they are cancer stem cells. Candidate epithelial and stromal stem/progenitor cells have been identified in mouse endometrium as label retaining cells (LRC) in the luminal epithelium and perivascular cells at the endometrial-myometrial junction, respectively (6). It is likely that endometrial stem/progenitor cells play key roles in the development of gynecological diseases associated with abnormal endometrial proliferation such as endometriosis and endometrial cancer (7).

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