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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)2988-3000
Antal sidor13
TidskriftCell Reports
Volym14
Utgivningsnummer12
StatusPublished - 2016
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Roman Galeev, 2018, Lund: Lund University, Faculty of Medicine. 127 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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