Scalable Generation of Pseudo-Unipolar Sensory Neurons from Human Pluripotent Stem Cells
Scalable Generation of Pseudo-Unipolar Sensory Neurons from Human Pluripotent Stem Cells
ABSTRACT Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types amenable for translational research. Here, we developed a highly efficient and reproducible method that differentiates hPSCs into peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10+ neural crest cells, followed by differentiation into sensory neurons with an in vivo-like pseudo-unipolar morphology. Detailed characterization confirmed that the hPSC-derived nociceptors displayed molecular and cellular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors, including critical pain-relevant drug targets (e.g., TRPV1, TAC1, CALCA, NAV1.7, NAV1.8). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.
Twumasi Prisca、Shim Jaehoon、Bean Bruce P.、Singe? Ilyas、Deng Tao、Weber Claire、Chu Pei-Hsuan、Ormanoglu Pinar、Simeonov Anton、Jo Sooyeon、Jayakar Selwyn、Zhang Han-Xiong Bear、Jovanovic Vukasin M.、Ryu Seungmi、Tristan Carlos A.、Woolf Clifford J.、Voss Ty C.
National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)F.M. Kirby Neurobiology Center, Boston Children?ˉs Hospital||Department of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)Department of Neurobiology, Harvard Medical SchoolF.M. Kirby Neurobiology Center, Boston Children?ˉs Hospital||Department of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)F.M. Kirby Neurobiology Center, Boston Children?ˉs Hospital||Department of Neurobiology, Harvard Medical SchoolNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation, Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH)
基础医学生物科学研究方法、生物科学研究技术神经病学、精神病学
Twumasi Prisca,Shim Jaehoon,Bean Bruce P.,Singe? Ilyas,Deng Tao,Weber Claire,Chu Pei-Hsuan,Ormanoglu Pinar,Simeonov Anton,Jo Sooyeon,Jayakar Selwyn,Zhang Han-Xiong Bear,Jovanovic Vukasin M.,Ryu Seungmi,Tristan Carlos A.,Woolf Clifford J.,Voss Ty C..Scalable Generation of Pseudo-Unipolar Sensory Neurons from Human Pluripotent Stem Cells[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2022.03.24.485622.点此复制
评论