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Vascularization of cardiac organoids controls the extracellular matrix environment and regulates organoid functionality

ABSTRACT: Vascularization of cardiac organoids controls the extracellular matrix environment and regulates organoid functionality

PROVIDER: PRJNA634359 | ENA |

REPOSITORIES: ENA

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Vascularization of cardiac organoids controls the extracellular matrix environment and regulates organoid functionality

Project description:Crosstalk between cardiac cells is critical during heart development but its role in organ maturation is still largely uncharacterised. Here, we show that endothelial cells increase the force of contraction and enhance the expression of mature sarcomeric proteins and extracellular matrix (ECM) components in human pluripotent stem cell derived cardiac organoids (hCO). Endothelial cells regulate cardiac maturation and function both directly through secretion of ECM molecules and indirectly via paracrine signaling. Laminin α5, an endothelial enriched ECM protein, was identified as a key regulator of cardiac maturation and contractility in vitro. In vivo loss-of-function studies in mice confirmed that Lama5 was required for myocardial expansion during heart development in vivo. In addition, paracrine PDGF signaling was identified as a mediator of increased ECM deposition and cardiac contractility in hCO. This study uncovers matrix regulatory functions of endothelial cells governing cardiac maturation and highlights the importance of multicellularity for organoid models.

2023-05-20 | GSE150998 | GEO

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoid

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to22 batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-01-31 | PXD023705 | Pride

Human telencephalic organoid development in the presence and absence of exogenous extracellular matrix

Project description:Human telencephalic organoid development in the presence and absence of exogenous extracellular matrix

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Exercise Training Remodels Inguinal White Adipose Tissue Through Adaptations in Innervation, Vascularization and the Extracellular Matrix

Project description:Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses we find that 11-days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition, increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.

2023-10-24 | PXD040894 | Pride

SB431452 affects extracellular matrix during induction of hiPSC-derived gastric organoid with muscularis mucosa

Project description:SB431452 affects extracellular matrix during induction of hiPSC-derived gastric organoid with muscularis mucosa

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The confined environment in microfluidic reveals a hidden role of self-organizing extracellular-matrix in hepatic commitment and organoid formation of hiPSCs

Project description:The specification of cell identity during human liver development is strictly controlled by extrinsic signals that restrict and define distinct cell fates. However, it is still not clear how cells, when exposed to exogenous signals, activate secretory cascades involving morphogens, growth factors and cytokines, extracellular matrix (ECM) deposition and remodeling, which are extremely relevant especially in 3D self-organizing system such as hepatic organoids. Here, we investigated how the proteins secreted by human pluripotent stem cells (hPSCs) in response to developmental exogenous signals affect the progression from endoderm to the hepatic lineage, including their competence to generate nascent hepatic organoids. By using a microfluidics-based approach coupled with SILAC-MS-based quantitative proteomic analysis we found high abundancy of ECM-associated proteins. Hepatocyte-like cells derived in microfluidics, where accumulation of cell-secreted proteins is enhanced up to 7-fold, showed organized deposition of COL1, FN, LAM and COL4, consistent with observations in human fetal liver at 8-15pcw. Further differentiation leads to a more mature hepatic transcriptomic signature and 1.5-fold higher ammonia detoxification capacity compared to conventional culture conditions. Hepatic committed cells in an early stage either derived in microfluidics and exposed to exogenous ECM stimuli show a significant higher potential for hepatic organoids formation. Nascent organoids can be rapidly expanded for several passages and further differentiated into functional hepatocytes. These results proved an additional control over the efficiency of hepatic organoid formation and differentiation for downstream applications.

2020-10-24 | GSE159926 | GEO

Proteomic analysis of glomerular organoid extracellular matrix

Project description:Introduction Points to consider adding: -The matrix in the kidney/glomerulus is specialised and complex with basement membrane structures in addition to interstitial matrix components. -The glomerular basement membrane undergoes change in isoform composition of key matrix components including type IV collagen and laminin. -The matrix composition of kidney organoids has not been yet been investigated in a global manner.

2019-01-03 | PXD012198 | Pride

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Project description:We established a platform for the brain organoid culture by using human decellularized brain extracellular matrix (BEM) and a microfluidic device. This engineering concept of reconstituting brain-mimetic microenvironments facilitates development of a reliable culture platform for brain organoids, enabling effective modeling and drug development.

2021-06-01 | GSE145386 | GEO

Human telencephalic organoid development in the presence and absence of exogenous extracellular matrix

Project description:Long-term culture of human telencephalic organoids cultured in the presence or absence of exogenous ECM. To evaluate how ECM supplementation influences organoid development, we supplied exogenous ECM in the form of Matrigel at the beginning of neuroepithelialisation (day 10, D10), either as a solid droplet that provides long-term exposure to a polymerized network of ECM proteins (droplet embedding - condition "drop" in the metadata table), or transiently dissolved in the culture medium (concentration of 2%V/V ) from D10 to D13 (liquid embedding - "liq"). These protocols were compared to one without exposure to exogenous ECM ("no"). Organoids were processed at 120 days of culture, when mature cortical tissue is present.

2023-10-25 | GSE220085 | GEO

Alpha-1 adrenergic signaling drives cardiac regeneration through activation of extracellular matrix remodeling transcriptional program in macrophages

Project description:Autonomic drive plays a pivotal role in cardiac regeneration. Sympathetic or cholinergic denervation impairs myocardial regrowth in neonatal mouse and zebrafish hearts. Here, we uncovered the mechanistic underpinning of adrenergic signaling in regenerative repair of the heart to be critically dependent on immunomodulation. Through pharmacological and genetic manipulations, we identified adrenergic receptor alpha-1 as a key regulator of macrophage phenotypic diversification following myocardial infarction in zebrafish. Single-cell transcriptomics revealed that the receptor signals activation of an ‘extracellular matrix remodeling’ transcriptional program characterized by upregulation of matrix proteins and matrix-modifying enzymes in a macrophage subset. Functionally, adrenergic receptor alpha-1-activated macrophages regulate fibrotic response of the heart by mediating collagenous extracellular matrix turnover and myofibroblast activation, allowing vascularization and cardiomyocyte cell cycle entry at the infarcted lesion. These findings not only unravel the mechanism of adrenergic signaling in macrophage phenotypic and functional determination, but also highlight the potential of neural modulation for regulation of fibrosis and coordination of myocardial regenerative response.

2023-09-21 | GSE205103 | GEO

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