Synthetic liver fibrotic niche extracts achieve in vitro hepatoblasts phenotype enhancement and expansion

Zhang, Yuying; Guo, Anqi; Lyu, Cheng; Bi, Ran; Wu, Zhaozhao; Li, Wenjing; Zhao, Peng; Niu, Yudi; Na, Jie; Xi, Jianzhong; Du, Yanan

doi:10.1016/j.isci.2021.103303

Cited by 2 publications

(5 citation statements)

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“…Developing efficient culture system for hESCs-derived zonated LSECs. The optimization of the method for differentiating LSECs from hESCs was based on previously published work (Gage et al, 2020;Koui et al, 2017;Zhang et al, 2021a;Zhang et al, 2021b). The basal culture medium used was a cost-effective, chemically defined homemade AATS medium, which consisted of RPMI 1640 supplemented with rice-derived recombinant human albumin, l-ascorbic acid 2-phosphate magnesium salt, human Apo-transferrin, and sodium selenite (Zhang et al, 2021a).…”

Section: Resultsmentioning

confidence: 99%

“…Atomic force microscopy (AFM) was utilized to measure the Young’s modulus, adhering to the same protocol detailed in our previously published work(Zhang et al, 2021b).…”

Section: Methods Detailsmentioning

confidence: 99%

“…For initiation of cell differentiation, hESCs were seeded at a density of 1.2 × 10ˆ5 cells per well of a 12-well plate in mTeSR1 essential medium containing 10 μM Y27632. hESC-derived endothelial cells induction was optimized based on the method described by Zhang et al (Zhang et al, 2021b) , employing AATS medium from Professor Na Jie's Laboratory, Tsinghua University. Initially, hESCs were differentiated into mesoderm cells by culturing in AATS medium supplemented with 5 ng/ml BMP4 for one day, followed by an additional two days with both 5 ng/ml BMP4 and 2 μM CHIR99021.…”

Section: Cell Culture and Differentiationmentioning

confidence: 99%

“…Electron microscopy was conducted using a Quanta 200 at an acceleration voltage of 5 keV and a working distance of 5 mm. Atomic force microscopy (AFM) was utilized to measure the Young's modulus, adhering to the same protocol detailed in our previously published work (Zhang et al, 2021b).…”

Section: Organoid Characterizationmentioning

confidence: 99%

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hESCs-derived organoids achieve liver zonation by LSEC modulation

Zhang,

Huang,

Sun

et al. 2024

Preprint

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Liver zonation, essential for diverse physiological functions, is lacking in existing organoid models, hindering their ability to recapitulate liver development and pathogenesis. Addressing this gap, we explored the feasibility of achieving zonated organoid by co-culturing human embryonic stem cells (hESCs) derived hepatocytes with hESCs derived liver sinusoidal endothelial cells (LSECs) exhibiting characteristics of either the liver lobule's pericentral (PC) or periportal (PP) regions. Introducing zonated LSECs with variable WNT2 signaling subtly regulate hepatocyte zonation, resulting in noticeable metabolic function changes. Considering the lipid metabolism variations in PC and PP organoids, we constructed biomimetic zonated non-alcoholic fatty liver disease (NAFLD) organoids and revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) target LSECs, but not hepatocytes, indicating potential therapeutic mechanisms of GLP-1RA in NAFLD alleviation. This study highlights the crucial role of non-parenchymal cells in organoids for recapitulating niche heterogeneity, offering further insights for drug discovery and in vitro modeling of organ heterogeneity.

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Section: Resultsmentioning

confidence: 99%

“…Atomic force microscopy (AFM) was utilized to measure the Young’s modulus, adhering to the same protocol detailed in our previously published work(Zhang et al, 2021b).…”

Section: Methods Detailsmentioning

confidence: 99%

Section: Cell Culture and Differentiationmentioning

confidence: 99%

Section: Organoid Characterizationmentioning

confidence: 99%

See 2 more Smart Citations