Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Stamouli, Christina A LU ; Degener, Alexander LU ; Cepeda-Prado, Efrain LU ; Bruzelius, Andreas LU ; Andersson, Emil LU orcid ; Giacomoni, Jessica LU ; Vorgeat, Aurélie Delphine ; Kidnapillai, Srisaiyini LU ; Klementieva, Oxana LU orcid and Parmar, Malin LU orcid , et al. (2026) In Science Advances 12(1).
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Interneurons/metabolism, Parvalbumins/metabolism, Cellular Reprogramming, Cell Lineage, Neuroglia/metabolism, Cell Differentiation, GABAergic Neurons/metabolism
in
Science Advances
volume
12
issue
1
article number
eadv0588
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:41477840
ISSN
2375-2548
DOI
10.1126/sciadv.adv0588
language
English
LU publication?
yes
id
bfe6734e-d6b6-4b1a-a098-f4fa1806cd5c
date added to LUP
2026-01-07 15:42:46
date last changed
2026-01-08 08:30:18
@article{bfe6734e-d6b6-4b1a-a098-f4fa1806cd5c,
  abstract     = {{<p>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.</p>}},
  author       = {{Stamouli, Christina A and Degener, Alexander and Cepeda-Prado, Efrain and Bruzelius, Andreas and Andersson, Emil and Giacomoni, Jessica and Vorgeat, Aurélie Delphine and Kidnapillai, Srisaiyini and Klementieva, Oxana and Parmar, Malin and Olariu, Victor and Rylander Ottosson, Daniella}},
  issn         = {{2375-2548}},
  keywords     = {{Humans; Interneurons/metabolism; Parvalbumins/metabolism; Cellular Reprogramming; Cell Lineage; Neuroglia/metabolism; Cell Differentiation; GABAergic Neurons/metabolism}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{A distinct lineage pathway drives parvalbumin chandelier cell fate in human interneuron reprogramming}},
  url          = {{http://dx.doi.org/10.1126/sciadv.adv0588}},
  doi          = {{10.1126/sciadv.adv0588}},
  volume       = {{12}},
  year         = {{2026}},
}