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AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of hematopoietic stem cells.
Manesia, Javed K; Maganti, Harinad B; Almoflehi, Sakhar; Jahan, Suria; Hasan, Tanvir; Pasha, Roya; McGregor, Chelsea; Dumont, Nellie; Laganière, Josée; Audet, Julie; Pineault, Nicolas.
Afiliación
  • Manesia JK; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada.
  • Maganti HB; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada; Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, ON, Canada.
  • Almoflehi S; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada; Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, ON, Canada.
  • Jahan S; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada; Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, ON, Canada.
  • Hasan T; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada; Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, ON, Canada.
  • Pasha R; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada.
  • McGregor C; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada.
  • Dumont N; Héma-Québec, Innovation, Québec, QC, Canada.
  • Laganière J; Héma-Québec, Innovation, Québec, QC, Canada.
  • Audet J; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
  • Pineault N; Canadian Blood Services, Centre for Innovation, Ottawa, ON, Canada; Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, ON, Canada. Electronic address: nicolas.pineault@blood.ca.
Cell Rep Methods ; 3(12): 100663, 2023 Dec 18.
Article en En | MEDLINE | ID: mdl-38070507
ABSTRACT
Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a stem cell agonist in AA2P and optimize a series of stem cell agonist cocktails (SCACs) to help promote robust expansion of human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention and function of immature HSPC. We show that AA2P-mediated HSPC expansion is driven through DNA demethylation leading to enhanced expression of AXL and GAS6. Further, we demonstrate that GAS6 enhances the serial engraftment activity of HSPCs and show that the GAS6/AXL pathway is critical for robust HSPC expansion.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Desmetilación del ADN Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Desmetilación del ADN Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article