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Senior Lecturer Victor Olariu, MSc, PhD. Photo

Victor Olariu

Senior lecturer

Senior Lecturer Victor Olariu, MSc, PhD. Photo

A distinct lineage pathway drives parvalbumin chandelier cell fate in human interneuron reprogramming

Author

  • Christina A Stamouli
  • Alexander Degener
  • Efrain Cepeda-Prado
  • Andreas Bruzelius
  • Emil Andersson
  • Jessica Giacomoni
  • Aurélie Delphine Vorgeat
  • Srisaiyini Kidnapillai
  • Oxana Klementieva
  • Malin Parmar
  • Victor Olariu
  • Daniella Rylander Ottosson
Show all

Summary, in English

Direct lineage reprogramming of glial cells to induced neurons has the potential for restoring brain circuits and function in neuronal disorders and states. We introduce three-dimensional (3D) human glia reprogramming into neurons with a GABAergic interneuron phenotype using stem cell-derived human glia. Single-nucleus RNA sequencing of the converted cells demonstrates distinct neuronal clusters within 2 weeks, including a parvalbumin (PV) cluster with high neuronal maturity and features of chandelier interneurons. A lineage trajectory analysis of the glia-to-neuron conversion reveals a distinct lineage pathway to PV chandelier fate, including various neuronal developmental stages and the establishment of synaptic machinery. This analysis reveals PV fate-important genes that are previously unknown to neural reprogramming with promising functional importance for future derivations. Our data demonstrate successful human glia conversion into interneurons with features of bona fide PV subtype and highlight the reprogramming trajectory with key transitional genes. This advancement holds promise for future human brain cell engineering and repair.

Department/s

  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • MultiPark: Multidisciplinary research on neurodegenerative diseases
  • Regenerative Neurophysiology
  • Stem Cell Center
  • Department of Earth and Environmental Sciences (MGeo)
  • Computational Science for Health and Environment
  • Centre for Environmental and Climate Science (CEC)
  • Developmental and Regenerative Neurobiology
  • Advanced Cancer
  • LU Profile Area: Light and Materials
  • LU Profile Area: Proactive Ageing
  • LTH Profile Area: Nanoscience and Semiconductor Technology
  • NanoLund: Centre for Nanoscience
  • Medical Microspectroscopy
  • BECC: Biodiversity and Ecosystem services in a Changing Climate
  • MERGE: ModElling the Regional and Global Earth system

Publishing year

2026-01-02

Language

English

Publication/Series

Science Advances

Volume

12

Issue

1

Document type

Journal article

Publisher

American Association for the Advancement of Science (AAAS)

Topic

  • Neurosciences

Keywords

  • Humans
  • Interneurons/metabolism
  • Parvalbumins/metabolism
  • Cellular Reprogramming
  • Cell Lineage
  • Neuroglia/metabolism
  • Cell Differentiation
  • GABAergic Neurons/metabolism

Status

Published

Research group

  • Regenerative Neurophysiology
  • Computational Science for Health and Environment
  • Developmental and Regenerative Neurobiology
  • Advanced Cancer
  • Medical Microspectroscopy

ISBN/ISSN/Other

  • ISSN: 2375-2548