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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
Publishing year: 2016
Language: English
Pages: 2988-3000
Publication/Series: Cell Reports
Volume: 14
Issue: 12
Document type: Journal article
Publisher: Cell Press

Abstract 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.

Keywords

  • Immunology in the medical area

Other

Published
  • ISSN: 2211-1247
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

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Project manager

Familial Breast Cancer

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Professor

Oncology and Pathology, MV

MV 404 C21C2

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