Charting the transition from in vitro gliogenesis to the in vivo maturation of human glial progenitor cells transplanted into the hypomyelinated mouse brain.

Authors

John N Mariani, Steven J Schanz, Benjamin Mansky, Xiaolu Wei, Carter C Long, Devin Chandler-Militello, Hannah E Aichelman, Nguyen P T Huynh, Steven A Goldman

Published in

Nature communications. Volume 17. Issue 1. Apr 23, 2026. Epub Apr 23, 2026.

Abstract

Neither rodent models nor in vitro studies of human cells adequately describe the molecular ontogeny of human glial progenitor cells (hGPCs). Here, we use scRNA-seq together with scATAC-Seq and CUT&TAG assessment of chromatin accessibility to track the in vitro genesis and in vivo differentiation of hGPCs from pluripotent stem cells (PSCs). In vitro, the hGPC pool comprises 4 transcriptionally distinct subpopulations, each associated with a distinct pattern of chromatin accessibility and histone modification of stage-dependent genes. After the neonatal transplant of these cells into myelin-deficient shiverer mice (MBP^shi/shi), they differentiate further as astrocytes and oligodendrocytes. A combination of gene co-expression, motif enrichment, cell-trajectory, cell-cell interaction, and spatial transcriptomic analyses reveals that the host environment potentiates the context-dependent differentiation of the hGPCs, via their activation of distinct gene regulatory networks. Together, these data describe the process and pathways by which human PSC-derived GPCs are generated in vitro and diversify in vivo to mature as astrocytes and oligodendrocytes.

PMID:
42026046
Bibliographic data and abstract were imported from PubMed on 14 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.