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In vitro atlas of dorsal spinal interneurons reveals Wnt signaling as a critical regulator of progenitor expansion.
Gupta, Sandeep; Kawaguchi, Riki; Heinrichs, Eric; Gallardo, Salena; Castellanos, Stephanie; Mandric, Igor; Novitch, Bennett G; Butler, Samantha J.
Afiliação
  • Gupta S; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: sandeepg
  • Kawaguchi R; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Heinrichs E; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Genetics and Genomics Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Gallardo S; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Interdepartmental Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Castellanos S; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; CIRM Bridges to Research Pro
  • Mandric I; Department of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Novitch BG; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Intellectual & Developme
  • Butler SJ; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Intellectual & Developme
Cell Rep ; 40(3): 111119, 2022 07 19.
Article em En | MEDLINE | ID: mdl-35858555
Restoring sensation after injury or disease requires a reproducible method for generating large quantities of bona fide somatosensory interneurons. Toward this goal, we assess the mechanisms by which dorsal spinal interneurons (dIs; dI1-dI6) can be derived from mouse embryonic stem cells (mESCs). Using two developmentally relevant growth factors, retinoic acid (RA) and bone morphogenetic protein (BMP) 4, we recapitulate the complete in vivo program of dI differentiation through a neuromesodermal intermediate. Transcriptional profiling reveals that mESC-derived dIs strikingly resemble endogenous dIs, with the correct molecular and functional signatures. We further demonstrate that RA specifies dI4-dI6 fates through a default multipotential state, while the addition of BMP4 induces dI1-dI3 fates and activates Wnt signaling to enhance progenitor proliferation. Constitutively activating Wnt signaling permits the dramatic expansion of neural progenitor cultures. These cultures retain the capacity to differentiate into diverse populations of dIs, thereby providing a method of increasing neuronal yield.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica no Desenvolvimento / Via de Sinalização Wnt Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica no Desenvolvimento / Via de Sinalização Wnt Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2022 Tipo de documento: Article