scholarly journals Mono- and multi-nucleated ventricular cardiomyocytes constitute a transcriptionally homogenous cell population

2019 ◽  
Vol 114 (5) ◽  
Author(s):  
Michail Yekelchyk ◽  
Stefan Guenther ◽  
Jens Preussner ◽  
Thomas Braun
Keyword(s):  
Cell Population ◽  
Ventricular Cardiomyocytes ◽  
Homogenous Cell Population

scholarly journals RUNX1 Mutations Cause a Myeloid Differentiation Block Leading to the Formation of a Long Term Expanding CD34+/CD33+/CD45RA+/CD123+ Cell Population

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1979-1979
Author(s):  
Myléne Gerritsen ◽  
Esther Tijchon ◽  
Amit Mandoli ◽  
Joost H.A. Martens ◽  
Jan Jacob Schuringa ◽  
...  
Keyword(s):  
Cell Population ◽  
Molecular Mechanisms ◽  
Myeloid Differentiation ◽  
Dominant Negative Mutant ◽  
Chip Sequencing ◽  
Cd34 Cells ◽  
Differentiation Block ◽  
Homogenous Cell Population

Abstract RUNX1 (AML1) is a transcription factor critically involved in normal haematopoiesis. Inactivating RUNX1 mutations have been frequently described in a variety of myeloid neoplasms, including high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Here, we aimed to functionally and molecularly define the actions of a dominant negative mutant by in vitro and in vivo experiments and RNA- and ChIP-sequencing approaches. Overexpression of the RUNX1 mutant S291fs300X in cord blood (CB) CD34+ cells caused a decline in erythroid colony formation (p= 0.01) while the CFU-GM colonies showed enhanced replating capacity compared to control (>3 times). It appeared that the replating potential was restricted to CD14-/CD15- progenitor cells. Long-term suspension cultures with myeloid growth factors (IL-3, SCF) of RUNX1 S291fs300X CB CD34+ cells provided a rather homogenous cell population after 10 weeks of culture. These cells are growth factor dependent and are phenotypically defined by CD34+/CD38+/CD33+/IL1-RAP+/CD45RA+/CD123+ resembling a GMP phenotype which can be propagated for approximately 20 weeks in suspension. Comparable results were obtained with normal bone marrow CD34+cells transduced with the RUNX1 S291fs300X. Karyotype analyses demonstrated no abnormalities while integration site analysis showed a variety of different integration sites and differences between individual samples, suggesting that the myeloid differentiation block is related to the RUNX1 S291fs300X mutation.Long-term MS5 stromal co-cultures of transduced RUNX1 S291fs300X CB CD34+ cells showed after 8-10 weeks a rather homogenous cell population with limited potential to expand and localized under the stromal layer. This cell population is phenotypically defined by CD34+/CD38-. The interactions with the stroma appear to prevent proliferation but retain quiescence, indicating that sufficient niche-cell interactions might be crucial for transformation. NSG mice experiments are performed to test the reproducibility of these findings in vivo. Q-PCR studies demonstrated reduced expression of C/EBPα in RUNX1 S291fs300X CB CD34+ cells, one of the key targets in myeloid differentiation. Therefore, week 10 RUNX1 S291fs300X CB CD34+ cells were transduced with a retroviral C/EBPα overexpression vector. The re-expression of C/EBPα resulted in a reduction in cell proliferation, decline of undifferentiated blasts and an increase in CD15 expression. RNA- and ChIP-sequencing data revealed a decreased expression of crucial RUNX1 target genes including C/EBPα and Cited2 and also a retained binding of mutant RUNX1 on these loci in conjunction with a decrease of H3K27ac. Further research into the molecular mechanisms by which this RUNX1 S291fs300Xderegulates gene-expression is in progress. Our results implicate that overexpression of RUNX1 S291fs300X mutant leads to impaired erythroid differentiation and a strong differentiation block of the myeloid lineage resulting in the expansion and maintenance of a GMP-like cell population. Disclosures No relevant conflicts of interest to declare.

Primary Dural Melanoma

Neurosurgery ◽  
1981 ◽  
Vol 9 (6) ◽  
pp. 710-717 ◽  
Author(s):  
Raj K. Naravan ◽  
Michael J. Rosner ◽  
John T. Povlishock ◽  
Alexander Girevendulis ◽  
Donald P. Becker
Keyword(s):  
Electron Microscopy ◽  
Cell Population ◽  
Cerebellopontine Angle ◽  
Tumor Recurrence ◽  
Concerted Effort ◽  
Mixed Cell ◽  
Mixed Cell Population ◽  
Homogenous Cell Population ◽  
Ultrastructural Findings ◽  
Electron Lucent

Abstract This study reviews the literature pertaining to primary meningeal melanoma and reports the clinical and ultrastructural findings in a case where the tumor appeared to be of pachymeningeal (dural) origin. This is clearly a departure from all previously described cases, in which a leptomeningeal (pial-arachnoidal) origin was either defined or assumed. Clinically. this case was remarkable in its rarity. its presentation as a cerebellopontine angle syndrome, and its occurrence in a Negro. a race in which melanomas are uncommon. Ultrastructurally. the tumor did demonstrate the presence of basement membrane abnormalities and numerous endothelial fenestrations. However, it was found to be made up of a homogenous cell population, consisting only of electron-lucent, melanin-laden cells. The mixed cell population noted previously in a primary leptomeningeal melanoma was not found in this tumor. In view of the fact that this patient continues to do well 1/12; years after operation, with no evidence of tumor recurrence, it is suggested that a homogenous cell population noted on electron microscopy could indicate a better prognosis. In addition, it may also indicate a pachymeningeal rather than a leptomeningeal origin for the tumor. A plea is made for greater specificity in terminology when describing primary meningeal melanomas and for a concerted effort to distinguish between those of dural and those of leptomeningeal origin.

Ultrastructural Changes in the Mammary Epithelial Cell Population During Neoplastic Development Induced by A Chemical Carcinogen.

1976 ◽  
Vol 34 ◽  
pp. 250-251 ◽  
Author(s):  
J. Russo ◽  
W. Isenberg ◽  
M. Ireland ◽  
I.H. Russo
Keyword(s):  
Mammary Gland ◽  
Cell Population ◽  
Virgin Female ◽  
Histological Change ◽  
Mammary Epithelial ◽  
Female Rats ◽  
Ultrastructural Changes ◽  
Post Inoculation ◽  
Chemical Carcinogen ◽  
Sprague Dawley

The induction of rat mammary carcinoma by the chemical carcinogen DMBA is used as a model for the study of the human disease (1). We previously described the histochemical changes that occur in the mammary gland of DMBA treated animals before the earliest manifested histological change, the intraductal proliferation (IDP), was observed (2). In the present work, we demonstrate that a change in the stable cell population found in the resting mammary gland occurs after carcinogen administration.Fifty-five day old Sprague-Dawley virgin female rats were inoculated intragastrically with 20mg of 7,12-dimethylbenz(a)anthracene (DMBA) in 1ml sesame oil. Non-inoculated, age-matched females were used as controls. Mammary glands from control and inoculated rats were removed weekly from the time of inoculation until 60 days post-inoculation. For electron microscopy, the glands were immersed in Karnovsky's fixative, post-fixed in 1% OsO4, dehydrated, and embedded in an Epon-Araldite mixture. Thick (lμ) sections were stained with 1% toluidine blue and were used for selecting areas for ultrastructural study.

The Responses of Cell Population in the Inferotemporal Cortex to Object Views with the Experience of Association Learning

2016 ◽  
Vol 136 (9) ◽  
pp. 1254-1260
Author(s):  
Reona Yamaguchi ◽  
Jun-ya Okamura ◽  
Kazunari Honda ◽  
Jin Oshima ◽  
Shintaro Saruwatari ◽  
...  
Keyword(s):  
Cell Population ◽  
Inferotemporal Cortex ◽  
Association Learning

Spindle Cell Carcinoma of the Tongue: Fallacies in Its Diagnosis

2018 ◽  
Vol 3 (02) ◽  
Author(s):  
Amrit Kaur Kaler, Shweta C, Smitha Chandra B.C, Rajeev Naik
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Cell Population ◽  
Squamous Cell ◽  
Spindle Cell ◽  
Spindle Cell Carcinoma ◽  
Biphasic Tumor ◽  
Carcinoma Of The Tongue ◽  
Ihc Markers

Spindle cell carcinoma is a rare aggressive biphasic tumor, composed of neoplastic proliferation of both epithelial (squamous) and spindle cell population. It constitutes about 1% of all oral cavity tumors 2a and is almost rare on the tongue; only few cases have been reported so far. This variant of squamous cell carcinoma, comprises major diagnostic problems due to its varied histomorphology and resemblance to sarcomatous lesion; hence diligent screening and IHC markers are mandatory for its diagnosis.

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