Connie Chen

Sanford-Burnham Medical Research Institute, لا هویا, California, United States

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Publications (3)21.09 Total impact

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    ABSTRACT: To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC), not the neural tube (NT). Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC)-secreted nitric oxide (NO) and direct contact with vascular smooth muscle cells (VSMCs) via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Stem Cell Reports 05/2015; 4(6). DOI:10.1016/j.stemcr.2015.04.013 · 5.64 Impact Factor
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    ABSTRACT: The transcription factor SRY (sex-determining region)-box 2 (SOX2) is an important functional marker of neural precursor cells (NPCs) and plays a critical role in self-renewal and neuronal differentiation; however, the molecular mechanisms underlying its functions are poorly understood. Using human embryonic stem cell-derived NPCs to model neurogenesis, we found that SOX2 is required to maintain optimal levels of LIN28, a well-characterized suppressor of let-7 microRNA biogenesis. Exogenous LIN28 expression rescued the NPC proliferation deficit, as well as the early but not the late stages of the neurogenic deficit associated with the loss of SOX2. We found that SOX2 binds to a proximal site in the LIN28 promoter region and regulates LIN28 promoter acetylation, likely through interactions with the histone acetyltransferase complex. Misexpression of let-7 microRNAs in NPCs reduced proliferation and inhibited neuronal differentiation, phenocopying the loss of SOX2. In particular, we identified let-7i as a novel and potent inhibitor of neuronal differentiation that targets MASH1 and NGN1, two well-characterized proneural genes. In conclusion, we discovered the SOX2-LIN28/let-7 pathway as a unique molecular mechanism governing NPC proliferation and neurogenic potential.
    Proceedings of the National Academy of Sciences 07/2013; 110(32). DOI:10.1073/pnas.1220176110 · 9.81 Impact Factor
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    ABSTRACT: Expression of MITF is often regarded as the key event in melanocyte specification from neural crest cells (Sommer, 2011). The central role of MITF in melanocyte biology and "phenotype-switching" in melanoma depending on the levels of MITF has been documented (Hoek and Goding 2010) and the importance of the fine-tuning of MITF levels in melanoma was proposed by several groups (Pinner et al., 2009; Shah et al., 2010). © 2012 John Wiley & Sons A/S.
    Pigment Cell & Melanoma Research 05/2012; 25(4):533-6. DOI:10.1111/j.1755-148X.2012.01012.x · 5.64 Impact Factor