Transcriptomics profiling of human PSC cultured under different conditions
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
Pseudo anonymized IDs of biological samples, sex
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
Language:
Method and outcome
Method and outcome
Population:
Donors of skin cells come from cohorts of patients in neurology, ASD, rare diseases, neurodevelopmental disorders, and healthy donors. The cells used in the study come from donor material collected from 2012 onwards from cohorts of 100-400 individuals collected in Sweden. Skin biopsies are collected from donors after informed consent for research on modeling early human development.
Study design:
- Preclinical study
Description of study design:
The purpose of the study was to see how much of the variation in gene expression can be explained by culture conditions, therefore comparisons have been made between as many cells as possible from different origins. The donor samples were reprogrammed into iPCS and transcriptome analyzes were performed to quality test the pluripotent stem cells. The establishment of iPSC has been done between 2012-2019.
Sampling procedure:
Description of sampling:
Not all donated cells were used for reprogramming because the process takes a long time and is very expensive. The selection of which donor cells were used for iPSC establishment was random and depended on available resources in terms of time and money. Data comes from men and women of different ages and this selection was also random and dependent on when we had resources. The data consists of 113 transcriptomes from 70 donors.
Data format/data structure:
Administrative information
Administrative information
Responsible department/unit:
Department of Neuroscience [C4]
Contributor(s):
Ethics Review:
Stockholm - 2012/208-31/3
Ethical approval for reprogramming of human cells where all samples have been taken from donors with approved informed consent.
Funding
Funding
Funding agency:
- Swedish Research Council
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Award number:
2017-03407_VR
Award title:
FATE CHOICES BY NEURAL STEM CELLS AND THE EFFECT ON PSYCHIATRIC DISORDERS
Funding information:
Psychiatric disorders are associated with mental, emotional, physical and economic burden to individuals, families and society. These diseases are poorly understood at the molecular level, however, psychiatric disorders are now believed to be neurodevelopmental disorders (NDD). Here we propose that there are common mechanisms of de-regulated neural stem cells causing a variety of psychiatric and NDD. Our proposed research will focus on elucidating how the neural stem cells make their fate choices, how they decide to self-renew or differentiation and how they decide what neural fate to differentiate into. We are building cellular models in vitro by using reprogrammed patient induced pluripotent stem cells (iPSc) differentiated to neural stem cells for our studies. Our preliminary data indicate that neural stem cells from patients with Down syndrome (DS) and Lissencephaly have a de-regulated exit from the stem cells state in opposing ways. Where, DS cells leave the stem cell state prematurely in contrast to Lissencaphaly cells that has a delayed differentiation start. Neural stem cells from patients with autism show a skewed fate choice between neuron and glia compared to healthy individuals. Here, we aim to pinpoint the underlying molecular mechanisms causing the de-regulated fate choices by the patient specific neural stem cells. Studies of these mechanisms would open up for discovery of common disease predictor, prevention and drug targets.
Funding agency:
- Swedish Research Council
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Award number:
2019-01498_VR
Award title:
Neural fate choices and the connection to psychiatric disorders
Funding information:
Here I propose a research program to address challenges and to approach molecular questions in psychiatric and neurodevelopmental disorders. Our main goal is to increase our understanding of neural stem cells and how they choose fate during early neuronal development in health and disease for future targeting therapies. We will address challenges like the lack of relevant human brain tissue to study and that animal models rarely mimic disease. To do this we are building cellular models of human brain development by reprogramming patient skin cells to induced pluripotent stem (iPS) cells that we further differentiate to neural stem cells and neurons in both 2D and 3D (organoids). During the establishment of my own research group we have derived and investigated cellular models of Lissencephaly, autism and schizophrenia, in which we have found de-regulated fate specification by neural stem cells causing skewed neuron to glia ratio and less mature neurons. Now, we will take these initial findings further by elucidate the mechanisms behind the skewed fate choices and especially study how cell surface molecules are involved. We will use iPS cells of patient and healthy individuals, brain organoids, single cell RNAseq, proteomics, cell polarity imaging, MEA, E-phys and calcium response to investigate the role of neural stem cells in psychiatric disorders and our hypothesis of common deregulated fate choosing mechanisms between various psychiatric disorders.
Funding agency:
Award number:
FO2019-0246
Award title:
Fate choice mechanisms by Neural Stem Cells causing Psychiatric Disorders
