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

Galeev, Roman (author): Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine

Baudet, Aurélie (author): Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine

Kumar, Praveen (author)

Rundberg Nilsson, Alexandra (author): Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine

Nilsson, Björn (author): Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine

Soneji, Shamit (author): Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine

Törngren, Therese (author): Lund University,Lunds universitet,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine

Borg, Åke (author): Lund University,Lunds universitet,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine

Kvist, Anders (author): Lund University,Lunds universitet,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine

Larsson, Jonas (author): Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine

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Abstract Subject headings

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.

By the author/editor: Galeev, Roman; Baudet, Aurélie; Kumar, Praveen; Rundberg Nilsson ...; Nilsson, Björn; Soneji, Shamit; show more...; Törngren, Theres ...; Borg, Åke; Kvist, Anders; Larsson, Jonas; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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