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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Genome-wide RNAi Screen Identifies Cohesin Genes as Modifiers of Renewal and Differentiation in Human HSCs

Author

  • Roman Galeev
  • Aurélie Baudet
  • Praveen Kumar
  • Alexandra Rundberg Nilsson
  • Björn Nilsson
  • Shamit Soneji
  • Therese Törngren
  • Åke Borg
  • Anders Kvist
  • Jonas Larsson

Summary, in English

To gain insights into the regulatory mechanisms of hematopoietic stem cells (HSCs), we employed a genome-wide RNAi screen in human cord-blood derived cells and identified candidate genes whose knockdown maintained the HSC phenotype during culture. A striking finding was the identification of members of the cohesin complex (STAG2, RAD21, STAG1, and SMC3) among the top 20 genes from the screen. Upon individual validation of these cohesin genes, we found that their knockdown led to an immediate expansion of cells with an HSC phenotype in vitro. A similar expansion was observed in vivo following transplantation to immunodeficient mice. Transcriptome analysis of cohesin-deficient CD34(+) cells showed an upregulation of HSC-specific genes, demonstrating an immediate shift toward a more stem-cell-like gene expression signature upon cohesin deficiency. Our findings implicate cohesin as a major regulator of HSCs and illustrate the power of global RNAi screens to identify modifiers of cell fate.

Department/s

  • Division of Molecular Medicine and Gene Therapy
  • Division of Molecular Hematology (DMH)
  • Division of Hematology and Transfusion Medicine
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Section V
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2016

Language

English

Pages

2988-3000

Publication/Series

Cell Reports

Volume

14

Issue

12

Document type

Journal article

Publisher

Cell Press

Topic

  • Immunology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 2211-1247