Astrocyte-oligodendrocyte crosstalk dependent myelination via secreted protein YKL40
- 1Virginia Commonwealth University
Abstract
Although oligodendrocyte differentiation and myelin formation are inherent properties of oligodendrocyte progenitor cells (OPCs) that are guided by intrinsic transcriptional and epigenetic programs, this process in the brain is finely regulated by signals coming from other cells, including astrocytes. Here, we identified the astrocyte secreted protein YKL40 at the center of astrocyte-OPC cross-communication and myelination in the developing brain. We find that YKL40 is expressed by astrocytes within white matter areas in the developing brain, coinciding with the OPC differentiation and myelination. Deletion of YKL40 in astrocytes showed delayed developmental myelination and reduced OPC proliferation. Interestingly, coculture with OPCs in vitro specifically induces YKL40 expression in astrocytes, which in turn promotes OPC differentiation and OPC proliferation. Mechanistically, purified YKL40 significantly induced the expression of transcription factors Olig2 and MYRF (Myeline regulatory factor) in OPCs. Therefore, we identified a novel mechanism of OPC-astrocyte crosscommunication dependent myelination by astrocytic YKL40 in the developing brain.
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BibTeX
@misc{dominguez2026astrocyteoligodendrocyte,
title = {{Astrocyte-oligodendrocyte crosstalk dependent myelination via secreted protein YKL40}},
author = {O. Dominguez and S. Munir and S. C. R. Thumu and C. Tuck and J. P. Gonzales and U. Oh and T. Kordula and B. Fuss and S. Singh},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750142},
url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750142v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Astrocyte-oligodendrocyte crosstalk dependent myelination via secreted protein YKL40
AU - O. Dominguez
AU - S. Munir
AU - S. C. R. Thumu
AU - C. Tuck
AU - J. P. Gonzales
AU - U. Oh
AU - T. Kordula
AU - B. Fuss
AU - S. Singh
PY - 2026
DA - 2026/09/08
PB - bioRxiv
DO - 10.64898/2026.09.08.750142
UR - https://www.biorxiv.org/content/10.64898/2026.09.08.750142v1
AB - Although oligodendrocyte differentiation and myelin formation are inherent properties of oligodendrocyte progenitor cells (OPCs) that are guided by intrinsic transcriptional and epigenetic programs, this process in the brain is finely regulated by signals coming from other cells, including astrocytes. Here, we identified the astrocyte secreted protein YKL40 at the center of astrocyte-OPC cross-communication and myelination in the developing brain. We find that YKL40 is expressed by astrocytes within white matter areas in the developing brain, coinciding with the OPC differentiation and myelination. Deletion of YKL40 in astrocytes showed delayed developmental myelination and reduced OPC proliferation. Interestingly, coculture with OPCs in vitro specifically induces YKL40 expression in astrocytes, which in turn promotes OPC differentiation and OPC proliferation. Mechanistically, purified YKL40 significantly induced the expression of transcription factors Olig2 and MYRF (Myeline regulatory factor) in OPCs. Therefore, we identified a novel mechanism of OPC-astrocyte crosscommunication dependent myelination by astrocytic YKL40 in the developing brain.
ER -