1. Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade.
- Author
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Khong DM, Dudakov JA, Hammett MV, Jurblum MI, Khong SM, Goldberg GL, Ueno T, Spyroglou L, Young LF, van den Brink MR, Boyd RL, and Chidgey AP
- Subjects
- Animals, Cell Count, Cell Movement, Cell Self Renewal, Gene Expression Profiling, Gene Expression Regulation, Developmental, Lymphoid Progenitor Cells cytology, Lymphoid Progenitor Cells metabolism, Male, Mice, Mice, Knockout, Models, Animal, Stem Cell Niche, Cell Differentiation genetics, Gonadal Steroid Hormones antagonists & inhibitors, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells metabolism, Lymphopoiesis physiology, Regeneration genetics
- Abstract
Mechanisms underlying age-related defects within lymphoid-lineages remain poorly understood. We previously reported that sex steroid ablation (SSA) induced lymphoid rejuvenation and enhanced recovery from hematopoietic stem cell (HSC) transplantation (HSCT). We herein show that, mechanistically, SSA induces hematopoietic and lymphoid recovery by functionally enhancing both HSC self-renewal and propensity for lymphoid differentiation through intrinsic molecular changes. Our transcriptome analysis revealed further hematopoietic support through rejuvenation of the bone marrow (BM) microenvironment, with upregulation of key hematopoietic factors and master regulatory factors associated with aging such as Foxo1. These studies provide important cellular and molecular insights into understanding how SSA-induced regeneration of the hematopoietic compartment can underpin recovery of the immune system following damaging cytoablative treatments. These findings support a short-term strategy for clinical use of SSA to enhance the production of lymphoid cells and HSC engraftment, leading to improved outcomes in adult patients undergoing HSCT and immune depletion in general., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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