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SUMMARY:Human cell fate engineering guided by single-cell transcriptomics 
 - Dr Hsiu-Chuan Lin (Centre for Genomic Regulation\, Barcelona)
DTSTART;VALUE=DATE-TIME:20260227T150000Z
DTEND;VALUE=DATE-TIME:20260227T160000Z
UID:https://talks.ox.ac.uk/talks/id/c0626739-e20c-4770-a600-b56f497a4063/
DESCRIPTION:Human neurons generated through transcription factor (TF) over
 expression have transformed the way we study neurodevelopment and model ne
 urological diseases\, opening new avenues for therapeutic discovery. Despi
 te this progress\, the full range of neuronal subtypes that can be program
 med in vitro remains largely uncharted. In this seminar\, I will talk abou
 t our work in expanding the diversity of neurons derived from human plurip
 otent stem cells by combining TF-driven reprogramming with systematic modu
 lation of developmental signaling pathways. We performed a large-scale scr
 een of 480 signaling conditions in parallel with NGN2 or ASCL1/DLX2 induct
 ion\, using multiplexed single-cell transcriptomics to capture cellular ou
 tcomes across 700\,000 cells. Our analysis revealed a broad spectrum of ex
 citatory and inhibitory neurons that align with the developmental patterni
 ng axes of the neural tube. Electrophysiological profiling showed that the
 se patterned neurons possess distinct functional and morphological propert
 ies shaped by their respective signaling environments. We perturbed TFs at
  the hub of gene regulatory networks (GRNs) and demonstrated their necessi
 ty and sufficiency to drive the specification of distinct neuronal subtype
 s. We further found that patterning neural progenitors before TF induction
  unlocks a greater range of neuronal diversity by activating regulons that
  mirror those of primary human neurons. Comparisons with primary tissue un
 covered closely matched neuronal subtypes sharing transcriptional signatur
 es in TF expression\, neurotransmitter usage\, and ion channel composition
 \, while highlighting persistent differences in metabolic pathways. Togeth
 er\, we put together an in vitro atlas of human neuronal diversity of over
  200 neuronal subtypes\, as well as providing a framework for programming 
 a wide array of human neurons and for understanding how transcriptional an
 d signaling cues cooperate to shape neuronal fate.\nSpeakers:\nDr Hsiu-Chu
 an Lin (Centre for Genomic Regulation\, Barcelona)
LOCATION:IMS-Tetsuya Nakamura Building (IDRM Seminar Rooms 1&2 or via Team
 s link)\, Roosevelt Dr\, Headington OX3 7TY
TZID:Europe/London
URL:https://talks.ox.ac.uk/talks/id/c0626739-e20c-4770-a600-b56f497a4063/
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DESCRIPTION:Talk:Human cell fate engineering guided by single-cell transcr
 iptomics - Dr Hsiu-Chuan Lin (Centre for Genomic Regulation\, Barcelona)
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