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  • 1.
    Schrenk-Siemens, Katrin
    et al.
    Heidelberg Univ, Germany.
    Pohle, Jörg
    Heidelberg Univ, Germany; Grunenthal GmbH, Germany.
    Rostock, Charlotte
    Heidelberg Univ, Germany.
    Abd El Hay, Muad
    Heidelberg Univ, Germany; Ernst Strungmann Inst, Germany.
    Lam, Ruby M.
    NIH, MD 20892 USA.
    Szczot, Marcin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. NIH, MD 20892 USA.
    Lu, Shiying
    Heidelberg Univ, Germany; Oliver Wyman GmbH, Germany.
    Chesler, Alexander T.
    NIH, MD 20892 USA.
    Siemens, Jan
    Heidelberg Univ, Germany.
    Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization2022Ingår i: Cells, E-ISSN 2073-4409, Vol. 11, nr 18, artikel-id 2905Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Somatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious perception turns into chronic pain. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. However, it is in particular the access to human pluripotent stem cells and the possibility of generating and studying human sensory neurons that has enriched the somatosensory research field. Based on our previous work, we describe here the generation of human stem cell-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations with different responsiveness to nociceptive stimuli such as capsaicin. Functional as well as deep sequencing analysis demonstrated that one protocol in particular allowed the generation of a mechano-nociceptive sensory neuron population, homogeneously expressing TRPV1. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation. The efficient and homogenous generation of these neurons make them an ideal translational tool to study mechanisms of sensitization, also in the context of chronic pain.

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  • 2.
    Szczot, Marcin
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. NIH, MD 20892 USA.
    Nickolls, Alec R.
    NIH, MD 20892 USA.
    Lam, Ruby M.
    NIH, MD 20892 USA; Brown Univ, RI 02912 USA.
    Chesler, Alexander T.
    NIH, MD 20892 USA; NINDS, MD 20892 USA.
    The Form and Function of PIEZO22021Ingår i: Annual Review of Biochemistry, ISSN 0066-4154, E-ISSN 1545-4509, Vol. 90, s. 507-534Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Mechanosensation is the ability to detect dynamic mechanical stimuli (e.g., pressure, stretch, and shear stress) and is essential for a wide variety of processes, including our sense of touch on the skin. How touch is detected and transduced at the molecular level has proved to be one of the great mysteries of sensory biology. A major breakthrough occurred in 2010 with the discovery of a family of mechanically gated ion channels that were coined PIEZOs. The last 10 years of investigation have provided a wealth of information about the functional roles and mechanisms of these molecules. Here we focus on PIEZO2, one of the two PIEZO proteins found in humans and other mammals. We review how work at the molecular, cellular, and systems levels over the past decade has transformed our understanding of touch and led to unexpected insights into other types of mechanosensation beyond the skin.

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