Asymmetric Notch activity by differential inheritance of lysosomes in human neural stem cells
Open accessAbstract
Symmetric and asymmetric cell divisions are conserved strategies for stem cell expansion and the generation of more committed progeny, respectively. Here, we demonstrate that in human neural stem cells (NSCs), lysosomes are asymmetrically inherited during mitosis. We show that lysosomes contain Notch receptors and that Notch activation occurs the acidic lysosome environment. The lysosome asymmetry correlates with the expression of the Notch target gene HES1 and the activity of Notch signaling in the daughter cells. Furthermore, an asymmetry of lysosomes and Notch receptors was also observed in a human organoid model of brain development with mitotic figures showing preferential inheritance of lysosomes and Notch receptor in that daughter cell remaining attached to the apical membrane. Thus, this study suggests a previously unknown function of lysosomes as a signaling hub to establish a bias in Notch signaling activity between daughter cells after an asymmetric cell division of human NSCs.
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Lysosome activity contributes to stemness; TFEB overexpression induces lysosomal biogenesis and suppresses differentiation, while knockdown of TFEB and TFE3 causes premature differentiation of NPCs.
“Lysosome activity more broadly contributes to stemness; if neuronal progenitor cells (NPCs) overexpress transcription factor EB (TFEB), this induces lysosomal biogenesis and differentiation is suppressed. Conversely, knockdown of TFEB and TFE3 causes premature differentiation of NPCs.19”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [19]
The Results section links lysosome inheritance in human neural stem cells to differences in Notch signaling, supporting the broad connection to progenitor-cell properties. But the passages on differentiation concern FGF2 withdrawal and Notch inhibition, not TFEB overexpression, lysosomal biogenesis, or TFEB/TFE3 knockdown; searches for those interventions found no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.85)
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- Authors
- Bohl, B., Jabali, A., Ladewig, J., & Koch, P.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Koch, Philipp
- Venue
- Science Advances
- Published
- 2022-02-11
- Volume
- 8
- Issue
- 6
- Pages
- eabl5792-eabl5792
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC8836802
- OpenAlex
- W4211264400
- Cited by
- 16
- References
- 33
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Science Advances (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- asymmetric cell division, Notch signaling, human neural stem cells, Hes1, lysosomal pH, Notch receptor, brain organoids, apical membrane
- MeSH terms
- Humans, Lysosomes, Mitosis, Signal Transduction, Receptors, Notch, Neural Stem Cells
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