Ziyan Xu

Duke University Hospital

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Alexandra Kuhlmann-Hogan

University of California, Los Angeles

Susan M. Kaech

Salk Institute for Biological Studies

Kacie A. Traina

Vanderbilt University Medical Center

Thekla Cordes

University of California, San Diego

Deborah Ayeni

Yale University

Christian M. Metallo

Salk Institute for Biological Studies

George Z. Cheng

Xinjiang Agricultural University

Reuben J. Shaw

Salk Institute for Biological Studies

Sandra L. Leibel

Rady Children's Hospital-San Diego

Katerina Politi

Yale Cancer Center

Cooperative Institutions

Fudan University

Salk Institute for Biological Studies

State Key Laboratory of Genetic Engineering

Zhongshan Hospital

Yale University

Nanjing Medical University

University of California, San Diego

University of Science and Technology of China

Chinese Academy of Sciences

Sun Yat-sen University

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Current knowledge on the multiform reconstitution of intestinal stem cell niche

World Journal of Stem Cells (2021)

Ziyan Xu Jinjian Huang Ye Liu Yun Zhao Xiuwen Wu

The development of "mini-guts" organoid originates from the identification of Lgr5+ intestinal stem cells (ISCs) and circumambient signalings within their specific niche at the crypt bottom. These in vitro self-renewing "mini-guts", also named enteroids or colonoids, undergo perpetual proliferation and regulated differentiation, which results in a high-performance, self-assembling and physiological organoid platform in diverse areas of intestinal research and therapy. The triumphant reconstitution of ISC niche in vitro also relies on Matrigel, a heterogeneous sarcoma extract. Despite the promising prospect of organoids research, their expanding applications are hampered by the canonical culture pattern, which reveals limitations such as inaccessible lumen, confine scale, batch to batch variation and low reproducibility. The tumor-origin of Matrigel also raises biosafety concerns in clinical treatment. However, the convergence of breakthroughs in cellular biology and bioengineering contribute to multiform reconstitution of the ISC niche. Herein, we review the recent advances in the microfabrication of intestinal organoids on hydrogel systems.

Matrigel

Organoid

Stem cell niche

LGR5

10.4252/wjsc.v13.i10.1564

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Citations (2)

Table S1 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth

Alexandra Kuhlmann-Hogan Thekla Cordes Ziyan Xu Ramya S. Kuna Kacie A. Traina

Table S1: BALF Patient Sample Clinical Features

Alveolar macrophage

10.1158/2159-8290.25730448

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Figure S1 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth

Alexandra Kuhlmann-Hogan Thekla Cordes Ziyan Xu Ramya S. Kuna Kacie A. Traina

Figure S1: Myeloid cell regulation during lung tumorigenesis.

Alveolar macrophage

10.1158/2159-8290.25730478.v1

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Figure S8 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth

Alexandra Kuhlmann-Hogan Thekla Cordes Ziyan Xu Ramya S. Kuna Kacie A. Traina

Figure S8: AMs transfer nutrients to tumor cells.

Alveolar macrophage

10.1158/2159-8290.25730457.v1

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Figure S4 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth

Alexandra Kuhlmann-Hogan Thekla Cordes Ziyan Xu Ramya S. Kuna Kacie A. Traina

Figure S4: Deficiency of PPARγ in CSF1R- or CD11c-expressing cells suppresses tumor growth.

Alveolar macrophage

10.1158/2159-8290.25730469.v1

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Supplementary Figure 4 from Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling

Ziyan Xu Alexandra Kuhlmann-Hogan Shihao Xu Hubert Tseng Dan Chen

Supplementary Figure 4

CD36

Scavenger Receptor

10.1158/0008-5472.28329172

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Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury

Bioactive Materials (2023)

Jinjian Huang Ziyan Xu Jiao Jiao Zongan Li Sicheng Li

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

Organoid

Hypoxia

Intestinal mucosa

10.1016/j.bioactmat.2023.07.001

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De Novo Screening and Mirror Image Isomerization of Linear Peptides Targeting α7 Nicotinic Acetylcholine Receptor

ACS Chemical Biology (2024)

Xiuxiu Cao Tianqi Liu Tao Wang Xudong Wang Ziyan Xu

As ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central and peripheral nervous systems and are associated with the pathogenesis of various degenerative neurological diseases. Here, we report the results of phage display-based de novo screening of an 11-residue linear peptide (named

10.1021/acschembio.3c00674

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Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds

RSC Advances (2019)

Tao Zheng Jinjian Huang Yungang Jiang Qinqing Tang Ye Liu

Wound infections bring huge challenges to clinical practice. A series of approaches are involved in the management of infected wounds including use of antibacterial agents, granulation tissue regeneration and scar prevention. In this study, we fabricated a sandwich-structure hydrogel dressing through layer-by-layer assembly of films and hydrogels. By pre-loading silver nanoparticles (AgNPs), vascular endothelial growth factors (VEGF) and ginsenoside Rg3 (Rg3) into each layer of the sandwich compound, this hydrogel could realize the sequential release of these drugs onto infected wound beds as demanded. Moreover, altering the thickness of middle layer could further change the drug delivery patterns characterized by delay at the initial releasing timepoint. When applying this dressing on infected wounds of rabbit ears, we found it could alleviate infection-induced inflammation, promote granulation tissue regeneration and inhibit scar formation. Collectively, the design of sandwich-structure hydrogels was facilitated to deliver specific drugs sequentially during their therapeutic time window for complicated diseases and has shown potential applications in infected wounds.

Granulation tissue

Granulation

Wound dressing

10.1039/c9ra09412a

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ZNF524 directly interacts with telomeric DNA and supports telomere integrity

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Hanna Braun Ziyan Xu Fiona Chang Nikenza Viceconte Grishma Rane

Abstract Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex blocks unwanted DNA damage repair at telomeres, e.g. by suppressing non-homologous end joining (NHEJ) through its subunit TRF2. We here describe ZNF524, a zinc finger protein that directly binds telomeric repeats with nanomolar affinity and reveal the base-specific sequence recognition by co-crystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, ZNF524 is a direct telomere-binding protein involved in the maintenance of telomere integrity.

Shelterin

Telomere-binding protein

Rap1

Nucleoprotein

10.1101/2022.11.30.518500

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Citations (2)