AA2P-mediated DNA Demethylation Synergizes with Stem Cell Agonists to Promote Expansion of Hematopoietic Stem Cells

Overview

Journal Cell Rep Methods

Specialty Cell Biology

Date 2023 Dec 9

PMID 38070507

Authors

Javed K Manesia

Harinad B Maganti

Sakhar Almoflehi

Suria Jahan

Tanvir Hasan

Roya Pasha

Chelsea McGregor

Nellie Dumont

Josee Laganiere

Julie Audet

Nicolas Pineault

Affiliations

Soon will be listed here.

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.

Citing Articles

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective.

Hasan T, Pasala A, Hassan D, Hanotaux J, Allan D, Maganti H Curr Oncol. 2024; 31(2):603-616.

PMID: 38392038 PMC: 10888387. DOI: 10.3390/curroncol31020044.

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