Publications by authors named "Shaghayegh Harbi"

5 Publications

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Adult Human Glioblastomas Harbor Radial Glia-like Cells.

Stem Cell Reports 2020 02 30;14(2):338-350. Epub 2020 Jan 30.

Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Single-cell RNA sequencing analyses of glioblastoma cells reveal transcriptionally dynamic clusters of RG-like cells that share the profiles of normal human fetal radial glia and that reside in quiescent and cycling states. Functional assays show a role for interleukin in triggering exit from dormancy into active cycling, suggesting a role for inflammation in tumor progression. These data are consistent with the possibility of persistence of RG into adulthood and their involvement in tumor initiation or maintenance. They also provide a putative cellular basis for the persistence of normal developmental programs in adult tumors.
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http://dx.doi.org/10.1016/j.stemcr.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014025PMC
February 2020

Beyond Serendipity to an Algorithmic Approach.

Plast Reconstr Surg Glob Open 2018 Feb 6;6(2):e1675. Epub 2018 Feb 6.

VasculoTox, Inc., New York, N.Y.; Department of Plastic Surgery, Kaiser Permanente, Irvine, Calif.; and Department of Epidemiology, University of California Irvine, School of Medicine, Irvine, Calif.

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http://dx.doi.org/10.1097/GOX.0000000000001675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865940PMC
February 2018

Arrested Development: Infantile Hemangioma and the Stem Cell Teratogenic Hypothesis.

Lymphat Res Biol 2017 06 18;15(2):153-165. Epub 2017 May 18.

4 Department of Medicine, New York University School of Medicine , New York, New York.

Background: Early-life programming is defined by the adaptive changes made by the fetus in response to an adverse in utero environment. Infantile hemangioma (IH), a vascular anomaly, is the most common tumor of infancy. Here we take IH as the tumor model to propose the stem cell teratogenic hypothesis of tumorigenesis and the potential involvement of the immune system.

Objectives: Teratogenic agents include chemicals, heavy metals, pathogens, and ionizing radiation. To investigate the etiology and pathogenesis of IH, we hypothesized that they result from a teratogenic mechanism. Immature, incompletely differentiated, dysregulated progenitor cells (multipotential stem cells) are arrested in development with vasculogenic, angiogenic, and tumorigenic potential due to exposure to teratogenic agents such as extrinsic factors that disrupt intrinsic factors via molecular mimicry. During the critical period of immunological tolerance, environmental exposure to immunotoxic agents may harness the teratogenic potential in the developing embryo or fetus and modify the early-life programming algorithm by altering normal fetal development, causing malformations, and inducing tumorigenesis. Specifically, exposure to environmental agents may interfere with physiological signaling pathways and contribute to the generation of IH, by several mechanisms.

Discussion: An adverse in utero environment no longer serves as a sustainable environment for proper embryogenesis and normal development. Targeted disruption of stem cells by extrinsic factors can alter the genetic program.

Conclusions: This article offers new perspectives to stimulate discussion, explore novel experimental approaches (such as immunotoxicity/vasculotoxicity assays and novel isogenic models), and to address the questions raised to convert the hypotheses into nontoxic, noninvasive treatments.
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http://dx.doi.org/10.1089/lrb.2016.0030DOI Listing
June 2017

Infantile Hemangioma Originates From A Dysregulated But Not Fully Transformed Multipotent Stem Cell.

Sci Rep 2016 10 27;6:35811. Epub 2016 Oct 27.

Department of Medicine, New York University School of Medicine, 550 First Avenue New York, NY 10016, USA.

Infantile hemangioma (IH) is the most common tumor of infancy. Its cellular origin and biological signals for uncontrolled growth are poorly understood, and specific pharmacological treatment is unavailable. To understand the process of hemangioma-genesis we characterized the progenitor hemangioma-derived stem cell (HemSC) and its lineage and non-lineage derivatives. For this purpose we performed a high-throughput (HT) phenotypic and gene expression analysis of HemSCs, and analyzed HemSC-derived tumorspheres. We found that IH is characterized by high expression of genes involved in vasculogenesis, angiogenesis, tumorigenesis and associated signaling pathways. These results show that IH derives from a dysregulated stem cell that remains in an immature, arrested stage of development. The potential biomarkers we identified can afford the development of diagnostic tools and precision-medicine therapies to "rewire" or redirect cellular transitions at an early stage, such as signaling pathways or immune response modifiers.
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http://dx.doi.org/10.1038/srep35811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081534PMC
October 2016