TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Meyers, Emily; Kessler, John A.

doi:10.1101/cshperspect.a022244

Cited by 137 publications

(119 citation statements)

References 301 publications

(265 reference statements)

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“…In the present study, we delved into the significance of Tgf-b signaling during various phases of regeneration. Importance of Tgf-b signaling during zebrafish retinal regeneration was intriguing mainly because this pathway was known to be anti-proliferative during neural development (Meyers and Kessler, 2017), cell differentiation (Moustakas et al, 2002), and cancer (Deng et al, 2013;Suzuki et al, 2010). In this study, we wanted to elucidate if the popularly known anti-proliferative function of Tgf-b signaling exists during zebrafish retinal regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Tgf-b signaling plays critical roles in cellular events such as embryonic development (Liu et al, 2018;Meyers and Kessler, 2017), homeostasis of hematopoietic stem cells (Blank and Karlsson, 2015), mesenchymal differentiation (Grafe et al, 2018), aging, and cancer (Papageorgis, 2017). Interestingly, modulation of the Tgf-b signaling in injured mice retina, with little regenerative capability, had a negligible effect on MG activation and regeneration (Kugler et al, 2015).…”

Section: Tgf-b Signaling Is Essential For Normal Retinal Regenerationmentioning

confidence: 99%

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Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Section: Tgf-b Signaling Is Essential For Normal Retinal Regenerationmentioning

confidence: 99%

Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish

et al. 2020

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“…5g). Bone morphogenetic protein (BMP) signaling, as part of the TGFβ signaling pathway, regulates cell fate determination and has a well-established role in neuronal differentiation 23 . To determine if BMP-receptor mediated activation of the TGFβ pathway in MCC cells would phenocopy LSD1 inhibition, we treated MCC cells with the ligands BMP2 or BMP4.…”

Section: And Extended Datamentioning

confidence: 99%

LSD1 inhibitors induce neuronal differentiation of Merkel cell carcinoma by disrupting the LSD1-CoREST complex and activating TGFβ signaling

Leiendecker

Jung

Neumann

et al. 2020

Preprint

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Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that is either associated with the clonal integration of the Merkel cell polyomavirus or with chronic sun exposure 1,2 . Immunotherapy is initially effective in many patients with metastatic MCC, but the response is rarely durable 3,4 . MCC lacks actionable mutations that could be utilized for targeted therapies, but epigenetic regulators, which govern cell fate, provide unexplored therapeutic entry points. Here, we performed a pharmacological screen in MCC cells, targeting epigenetic regulators. We discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. HMG20B (BRAF35), a poorly characterized subunit of the LSD1-CoREST complex, is also essential for MCC proliferation. LSD1 inhibition in MCC disrupts the LSD1-CoREST complex, directly induces the expression of key regulators of the neuronal lineage and of members of the TGFβ pathway, and activates a gene expression signature corresponding to normal Merkel cells. Our results provide a rationale for evaluating LSD1 inhibitors, which are currently being tested in patients with leukemia and solid tumors, in MCC.

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“…The ability to monitor internal cellular biomarkers at different time points and measure their changes over time is key to understanding the fundamental mechanisms governing dynamic cellular processes such as differentiation, maturation and ageing [1][2][3]. Temporal measurement of intracellular contents at the single-cell level can provide insights into the involved regulatory pathways and help understand the pathophysiology of disorders such as Alzheimer's and Parkinson's as well as the efficacy of drugs and their possible toxic effects [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

A Combined Numerical and Experimental Investigation of Localized Electroporation-based Transfection and Sampling

Mukherjee¹,

Nathamgari²,

Kessler³

et al. 2018

Preprint

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Localized electroporation has evolved as an effective technology for the delivery of foreign molecules into adherent cells, and more recently, for the sampling of cytosolic content from a small population of cells. Unlike bulk electroporation, where the electric field is poorly controlled, localized electroporation benefits from the spatial localization of the electric field on a small areal fraction of the cell membrane, resulting in efficient molecular transport and high cell-viability.Although there have been numerous experimental reports, a mechanistic understanding of the different parameters involved in localized electroporation is lacking. In this work, we developed a multiphysics model that a) predicts the electro-pore distribution in response to the local transmembrane potential and b) calculates the molecular transport into and out of the cell based on the predicted pore-sizes. Using the model, we identify that cell membrane tension plays a crucial role in enhancing both the amount and the uniformity of molecular transport, particularly for large proteins and plasmids. We qualitatively validate the model predictions by delivering large molecules (fluorescent-tagged bovine serum albumin and mCherry encoding plasmid) and by sampling an exogeneous protein (tdTomato) in an engineered cell line. The findings presented here should inform the future design of microfluidic devices for localized electroporation based sampling, eventually paving the way for temporal, single-cell analysis.

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TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Cited by 137 publications

References 301 publications

Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish

Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish

LSD1 inhibitors induce neuronal differentiation of Merkel cell carcinoma by disrupting the LSD1-CoREST complex and activating TGFβ signaling

A Combined Numerical and Experimental Investigation of Localized Electroporation-based Transfection and Sampling

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