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miRStem

Reprogramming of elite B cells to induced hematopoietic stem cell with microRNAs and transcription factors

Total Cost €

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EC-Contrib. €

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Partnership

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Project "miRStem" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO CENTRE DE REGULACIO GENOMICA 

Organization address
address: CARRER DOCTOR AIGUADER 88
city: BARCELONA
postcode: 8003
website: www.crg.es

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Project website https://thomas-graf-lab.com/
 Total cost 158˙121 €
 EC max contribution 158˙121 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2019-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO CENTRE DE REGULACIO GENOMICA ES (BARCELONA) coordinator 158˙121.00

Map

 Project objective

Generating Hematopoietic Stem Cells (HSCs) by Transcription Factor (TF) overexpression is of great interest in the stem cell field and promises considerable therapeutic potential. Among the systems described so far only one study, using murine B cells, has led to the generation of transplantable induced HSCs (iHSCs), although at exceedingly low efficiencies and using combinations between 6 and 8 TFs. We propose here a new approach to generate iHSCs based on the use of newly identified highly plastic “elite” type cells for reprogramming by the Yamanaka factors into induced pluripotent stem cells, generated by the transient exposure of B cells to C/EBPα. Hypothesizing that microRNAs could potentiate the effect of TFs in HSC reprogramming we will also analyze the effects of microRNA overexpression. For this we will first analyze HSCs and different hematopoietic progenitors to identify differentially expressed microRNAs. Different combinations of selected microRNAs will be cloned into inducible retroviral vectors together with hematopoietic TFs and used to infect “elite” CEBPα-primed B cells to screen for the induction, in vitro and in vivo, of iHSCs. The use of colony assays, cell surface marker and transcriptomic analyses of the resulting cells, as well as transplantation into irradiated mice, will enable us to identify microRNAs and TFs combinations that induce HSC reprogramming. The heterogeneity of iHSCs will then be tested by single cell expression analysis using RNA-seq. This project will provide new insights into the reprogramming of HSCs, the clinically most important type of adult stem cells, with potential medical applications. The proposed action will benefit the applicant’s career through acquisition of scientific maturity and independence.

 Publications

year authors and title journal last update
List of publications.
2019 Tian V. Tian, Bruno Di Stefano, Grégoire Stik, Maria Vila-Casadesús, José Luis Sardina, Enrique Vidal, Alessandro Dasti, Carolina Segura-Morales, Luisa De Andrés-Aguayo, Antonio Gómez, Johanna Goldmann, Rudolf Jaenisch, Thomas Graf
Whsc1 links pluripotency exit with mesendoderm specification
published pages: 824-834, ISSN: 1465-7392, DOI: 10.1038/s41556-019-0342-1
Nature Cell Biology 21/7 2020-01-16
2018 Gregoire Stik, Thomas Graf
Hoxb5, a Trojan horse to generate T cells
published pages: 210-212, ISSN: 1529-2908, DOI: 10.1038/s41590-018-0053-y
Nature Immunology 19/3 2020-01-16

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