IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60194-6.html
   My bibliography  Save this article

Human endothelial cells promote a human neural stem cell type B phenotype via Notch signaling

Author

Listed:
  • Brenda Gutierrez

    (University of California Irvine
    University of California Irvine)

  • Tzu Chia Liu

    (University of California Irvine
    University of California Irvine)

  • Carly Rodriguez

    (University of California Irvine)

  • Oier Pastor-Alonso

    (University of California San Francisco)

  • Hannah Lambing

    (University of California San Francisco)

  • Mercedes F. Paredes

    (University of California San Francisco)

  • Lisa A. Flanagan

    (University of California Irvine
    University of California Irvine
    University of California Irvine
    University of California Irvine)

Abstract

Neural stem and progenitor cell (NSPC) and vessel-forming endothelial cell (EC) communication throughout development and adulthood is vital for normal brain function. However, much remains unclear regarding coordinated regulation of these cells, particularly in humans. We find that contact with hECs increases hNSPC type B cells, which are GFAP-expressing adult NSPCs in the subventricular zone (SVZ), leading to generation of a human type B single-cell RNA sequencing (scRNAseq) dataset. Differential gene expression demonstrates an increase in Notch downstream mediators in type B hNSPCs after hEC contact. Blocking hNSPC Notch signaling, and reducing hEC expression of the Notch ligand DLL4, abrogates the effect of hECs on type B hNSPCs. We identify S100A6 and LeX as human type B cell markers, and analysis of the postnatal human SVZ confirms co-expression of GFAP, SOX2, S100A6, LeX and PROM1 in type B cells. Sites of contact are identified between type B hNSPCs and vasculature in the SVZ, providing evidence of human type B cell contact with hECs in the postnatal human brain. Thus, hEC contact promotes human type B cells via Notch signaling and these cells are in contact in stem cell niches in the human brain.

Suggested Citation

  • Brenda Gutierrez & Tzu Chia Liu & Carly Rodriguez & Oier Pastor-Alonso & Hannah Lambing & Mercedes F. Paredes & Lisa A. Flanagan, 2025. "Human endothelial cells promote a human neural stem cell type B phenotype via Notch signaling," Nature Communications, Nature, vol. 16(1), pages 1-25, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60194-6
    DOI: 10.1038/s41467-025-60194-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60194-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60194-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yujin Harada & Mayumi Yamada & Itaru Imayoshi & Ryoichiro Kageyama & Yutaka Suzuki & Takaaki Kuniya & Shohei Furutachi & Daichi Kawaguchi & Yukiko Gotoh, 2021. "Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    2. Aparna Bhaduri & Carmen Sandoval-Espinosa & Marcos Otero-Garcia & Irene Oh & Raymund Yin & Ugomma C. Eze & Tomasz J. Nowakowski & Arnold R. Kriegstein, 2021. "An atlas of cortical arealization identifies dynamic molecular signatures," Nature, Nature, vol. 598(7879), pages 200-204, October.
    3. Frank Bicker & Verica Vasic & Guilherme Horta & Felipe Ortega & Hendrik Nolte & Atria Kavyanifar & Stefanie Keller & Nevenka Dudvarski Stankovic & Patrick N. Harter & Rui Benedito & Beat Lutz & Tobias, 2017. "Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    4. Nader Sanai & Thuhien Nguyen & Rebecca A. Ihrie & Zaman Mirzadeh & Hui-Hsin Tsai & Michael Wong & Nalin Gupta & Mitchel S. Berger & Eric Huang & Jose-Manuel Garcia-Verdugo & David H. Rowitch & Arturo , 2011. "Corridors of migrating neurons in the human brain and their decline during infancy," Nature, Nature, vol. 478(7369), pages 382-386, October.
    5. Nader Sanai & Anthony D. Tramontin & Alfredo Quiñones-Hinojosa & Nicholas M. Barbaro & Nalin Gupta & Sandeep Kunwar & Michael T. Lawton & Michael W. McDermott & Andrew T. Parsa & José Manuel-García Ve, 2004. "Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration," Nature, Nature, vol. 427(6976), pages 740-744, February.
    6. Gioele La Manno & Kimberly Siletti & Alessandro Furlan & Daniel Gyllborg & Elin Vinsland & Alejandro Mossi Albiach & Christoffer Mattsson Langseth & Irina Khven & Alex R. Lederer & Lisa M. Dratva & An, 2021. "Molecular architecture of the developing mouse brain," Nature, Nature, vol. 596(7870), pages 92-96, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiangling Feng & Yingjie Gao & Fan Chu & Yuwen Shan & Meicheng Liu & Yaoyi Wang & Ying Zhu & Qing Lu & Mingfeng Li, 2025. "Cortical arealization of interneurons defines shared and distinct molecular programs in developing human and macaque brains," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. Jia-Ru Wei & Zhao-Zhe Hao & Chuan Xu & Mengyao Huang & Lei Tang & Nana Xu & Ruifeng Liu & Yuhui Shen & Sarah A. Teichmann & Zhichao Miao & Sheng Liu, 2022. "Identification of visual cortex cell types and species differences using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    3. Wei Zhou & Cheng Xu & Shuangrui Yang & Haocheng Li & Changcun Pan & Zhuang Jiang & Luyang Xie & Xiaohan Li & Huimin Qiao & Da Mi & Yujie Tang & Liwei Zhang & Qiaoran Xi, 2025. "An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    4. Michael R. Williamson & Stephanie P. Le & Ronald L. Franzen & Nicole A. Donlan & Jill L. Rosow & Mathilda S. Nicot-Cartsonis & Alexis Cervantes & Benjamin Deneen & Andrew K. Dunn & Theresa A. Jones & , 2023. "Subventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Erica Butti & Stefano Cattaneo & Marco Bacigaluppi & Marco Cambiaghi & Giulia Maria Scotti & Elena Brambilla & Francesca Ruffini & Giacomo Sferruzza & Maddalena Ripamonti & Fabio Simeoni & Laura Cacci, 2022. "Neural precursor cells tune striatal connectivity through the release of IGFBPL1," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    6. Haier, Richard J., 2021. "Are we thinking big enough about the road ahead? Overview of the special issue on the future of intelligence research," Intelligence, Elsevier, vol. 89(C).
    7. Joachim Jonghe & Tomasz S. Kaminski & David B. Morse & Marcin Tabaka & Anna L. Ellermann & Timo N. Kohler & Gianluca Amadei & Charlotte E. Handford & Gregory M. Findlay & Magdalena Zernicka-Goetz & Sa, 2023. "spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. G. Ball & S. Oldham & V. Kyriakopoulou & L. Z. J. Williams & V. Karolis & A. Price & J. Hutter & M. L. Seal & A. Alexander-Bloch & J. V. Hajnal & A. D. Edwards & E. C. Robinson & J. Seidlitz, 2024. "Molecular signatures of cortical expansion in the human foetal brain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. E. P. Tissink & A. A. Shadrin & D. Meer & N. Parker & G. Hindley & D. Roelfs & O. Frei & C. C. Fan & M. Nagel & T. Nærland & M. Budisteanu & S. Djurovic & L. T. Westlye & M. P. Heuvel & D. Posthuma & , 2024. "Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Yingfeng Tao & Xiaoliu Zhou & Leqiang Sun & Da Lin & Huaiyuan Cai & Xi Chen & Wei Zhou & Bing Yang & Zhe Hu & Jing Yu & Jing Zhang & Xiaoqing Yang & Fang Yang & Bang Shen & Wenbao Qi & Zhenfang Fu & J, 2023. "Highly efficient and robust π-FISH rainbow for multiplexed in situ detection of diverse biomolecules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Hongwon Kim & Byounggook Cho & Hyung Kyu Kim & Soi Kang & Saemin An & Daeyeol Kwon & Hee Young Kim & Jongpil Kim, 2025. "PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    12. Jonathan M Werner & Jesse Gillis, 2024. "Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue," PLOS Biology, Public Library of Science, vol. 22(12), pages 1-34, December.
    13. Allen Yen & Simona Sarafinovska & Xuhua Chen & Dominic D. Skinner & Fatjon Leti & MariaLynn Crosby & Jessica Hoisington-Lopez & Yizhe Wu & Jiayang Chen & Zipeng A. Li & Kevin K. Noguchi & Robi D. Mitr, 2024. "MYT1L deficiency impairs excitatory neuron trajectory during cortical development," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Wei Liu & Xu Liao & Ziye Luo & Yi Yang & Mai Chan Lau & Yuling Jiao & Xingjie Shi & Weiwei Zhai & Hongkai Ji & Joe Yeong & Jin Liu, 2023. "Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Abhijit Chakraborty & Jeffrey G. Wang & Ferhat Ay, 2022. "dcHiC detects differential compartments across multiple Hi-C datasets," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    16. Naohiro Kuwayama & Tomoya Kujirai & Yusuke Kishi & Rina Hirano & Kenta Echigoya & Lingyan Fang & Sugiko Watanabe & Mitsuyoshi Nakao & Yutaka Suzuki & Kei-ichiro Ishiguro & Hitoshi Kurumizaka & Yukiko , 2023. "HMGA2 directly mediates chromatin condensation in association with neuronal fate regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Hao Xu & Shuyan Wang & Minghao Fang & Songwen Luo & Chunpeng Chen & Siyuan Wan & Rirui Wang & Meifang Tang & Tian Xue & Bin Li & Jun Lin & Kun Qu, 2023. "SPACEL: deep learning-based characterization of spatial transcriptome architectures," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    18. Akram A. Hamed & Daniel J. Kunz & Ibrahim El-Hamamy & Quang M. Trinh & Omar D. Subedar & Laura M. Richards & Warren Foltz & Garrett Bullivant & Matthaeus Ware & Maria C. Vladoiu & Jiao Zhang & Antony , 2022. "A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    19. Rebecca Sebastian & Kang Jin & Narciso Pavon & Ruby Bansal & Andrew Potter & Yoonjae Song & Juliana Babu & Rafael Gabriel & Yubing Sun & Bruce Aronow & ChangHui Pak, 2023. "Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Vanessa Donega & Astrid T. Geest & Jacqueline A. Sluijs & Roland E. Dijk & Chi Chiu Wang & Onur Basak & R. Jeroen Pasterkamp & Elly M. Hol, 2022. "Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60194-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.