Dataset Information

Wnt-modulated hiPSC-derived insulin-producing cells, adult human islet proteome

ABSTRACT: We aimed to assess whether Wnt-modulation could contribute to mature hiPSC-derived insulin-producing cells in vitro. Building our hypothesis on our previous findings of Wnt activation in immature hiPSC-derived insulin-producing cells compared to adult human islets and with recent data reporting a link between Wnt/PCP and in vitro beta-cell maturation. In this study we stimulated hiPSC-derived insulin-producing cells with syntetic proteins including WNT3A, WNT4, WNT5A and WNT5B as well as inhibiting endogeneous Wnt signaling with Tankyrase inhibitor G007-LK.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Islet Of Langerhans, Cell Culture

SUBMITTER: Heidrun Vethe

LAB HEAD: Helge Ræder

PROVIDER: PXD012081 | Pride | 2019-11-13

REPOSITORIES: Pride

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Publications

The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.

Vethe Heidrun H Ghila Luiza L Berle Magnus M Hoareau Laurence L Haaland Øystein A ØA Scholz Hanne H Paulo Joao A JA Chera Simona S Ræder Helge H

Frontiers in endocrinology 20190508

Current published protocols for targeted differentiation of human stem cells toward pancreatic β-cells fail to deliver sufficiently mature cells with functional properties comparable to human islet β-cells. We aimed to assess whether Wnt-modulation could promote the final protocol stages of β-cell maturation, building our hypothesis on our previous findings of Wnt activation in immature hiPSC-derived stage 7 (S7) cells compared to adult human islets and with recent data reporting a link between ...[more]

PMID: 31139151

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Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the âageâ of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031). 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.

Dataset Information

Wnt-modulated hiPSC-derived insulin-producing cells, adult human islet proteome

Publications

The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.

Similar Datasets

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