miR-99 regulates normal and malignant hematopoietic stem cell self-renewal Journal Article

Authors: Khalaj, M.; Woolthuis, C. M.; Hu, W.; Durham, B. H.; Chu, S. H.; Qamar, S.; Armstrong, S. A.; Park, C. Y.
Article Title: miR-99 regulates normal and malignant hematopoietic stem cell self-renewal
Abstract: The microRNA-99 (miR-99) family comprises a group of broadly conserved microRNAs that are highly expressed in hematopoietic stem cells (HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny. Herein, we show that miR-99 regulates self-renewal in both HSCs and LSCs. miR-99 maintains HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants. Confirming miR-99's role in established AML, miR-99 inhibition induced primary AML patient blasts to undergo differentiation. A forward genetic shRNA library screen revealed Hoxa1 as a critical mediator of miR-99 function in HSC maintenance, and this observation was independently confirmed in both HSCs and LSCs. Together, these studies demonstrate the importance of noncoding RNAs in the regulation of HSC and LSC function and identify miR-99 as a critical regulator of stem cell self-renewal. © 2017 Khalaj et al.
Journal Title: Journal of Experimental Medicine
Volume: 214
Issue: 8
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2017-08-01
Start Page: 2453
End Page: 2470
Language: English
DOI: 10.1084/jem.20161595
PROVIDER: scopus
PMCID: PMC5551568
PUBMED: 28733386
Notes: Article -- Export Date: 5 September 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Wenhuo Hu
    48 Hu
  2. Mona   Khalaj
    8 Khalaj
  3. Benjamin Heath Durham
    85 Durham
  4. Sarah Qamar
    2 Qamar