Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells
Jennifer L. Gori, … , Shahin Rafii, Hans-Peter Kiem
Jennifer L. Gori, … , Shahin Rafii, Hans-Peter Kiem
Published February 9, 2015
Citation Information: J Clin Invest. 2015;125(3):1243-1254. https://doi.org/10.1172/JCI79328.
View: Text | PDF
Technical Advance Article has an altmetric score of 56

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

  • Text
  • PDF
Abstract

Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC–derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina–induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34+CD45+ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain–null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood–derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34+ cells, suggesting these ligands are critical for HSC emergence.

Authors

Jennifer L. Gori, Jason M. Butler, Yan-Yi Chan, Devikha Chandrasekaran, Michael G. Poulos, Michael Ginsberg, Daniel J. Nolan, Olivier Elemento, Brent L. Wood, Jennifer E. Adair, Shahin Rafii, Hans-Peter Kiem

×

Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 Total
Citations: 3 3 1 7 5 9 8 9 20 7 72
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2015 (7)

Title and authors Publication Year
G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
P Zhang, Q He, D Chen, W Liu, L Wang, C Zhang, D Ma, W Li, B Liu, F Liu
Cell Research 2015
Transplantation of Macaca cynomolgus iPS-derived hematopoietic cells in NSG immunodeficient mice
S Abed, A Tubsuwan, P Chaichompoo, IH Park, A Pailleret, A Benyoucef, L Tosca, ED Dreuzy, A Paulard, M Granger-Locatelli, F Relouzat, S Prost, G Tachdjian, S Fucharoen, GQ Daley, E Payen, S Chretien, P Leboulch, L Maouche-Chretien
Haematologica 2015
Lost in translation: pluripotent stem cell-derived hematopoiesis
M Ackermann, S Liebhaber, JH Klusmann, N Lachmann
EMBO Molecular Medicine 2015
Definitive Hematopoietic Multipotent Progenitor Cells Are Transiently Generated From Hemogenic Endothelial Cells in Human Pluripotent Stem Cells: HEMATOPOIETIC MPP GENERATION FROM hPSCs
H Bai, Y Liu, Y Xie, DL Hoyle, RA Brodsky, L Cheng, T Cheng, ZZ Wang
Journal of Cellular Physiology 2015
Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering
J Lowenthal, S Gerecht
Biochemical and Biophysical Research Communications 2015
Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and Genome Engineering
M Jung, CE Dunbar, T Winkler
Molecular Therapy 2015
Hematopoietic stem cell expansion and generation: the ways to make a breakthrough
B Park, KH Yoo, C Kim
Blood Research 2015

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 4 news outlets
Blogged by 2
Posted by 10 X users
Referenced in 5 patents
On 3 Facebook pages
Mentioned in 1 Google+ posts
Reddited by 1
Highlighted by 1 platforms
168 readers on Mendeley
See more details