Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis. Blockade of Chrm1 in the CNS, but not the periphery, reduces HSC mobilization. Mobilization is impaired in Chrm1 mice and rescued by parabiosis with wild-type mice, suggesting a relay by a blood-borne factor. We have identified the glucocorticoid (GC) hormones as critical for optimal mobilization. Physiological levels of corticosterone promote HSC migration via the GC receptor Nr3c1-dependent signaling and upregulation of actin-organizing molecules. These results uncover long-range regulation of HSC migration emerging from the brain.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467872 | PMC |
| http://dx.doi.org/10.1016/j.stem.2017.01.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury.
Bioact Mater
March 2025
Tianjin Key Laboratory of Spine and Spinal Cord, International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedics, International Chinese Musculoskeletal Research Society Collaborating Center for Spinal Cord Injury, Tianjin Medical University General Hospital, Tianjin, 300070, China.
Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries.
View Article and Find Full Text PDFPlerixafor in association with R-DHAP and G-CSF to mobilize a large number of CD34 + cells in patients with relapsed-refractory diffuse large B-cell lymphomas.
Ann Hematol
December 2024
Hematology and Transplant Unit, "Cardinal Panico" Hospital, Tricase, LE, Italy.
Lymphoma and plasma cell disorders are the most common indications for autologous hematopoietic stem cell (HSC) transplantation. We conducted a prospective multicenter study with the aim of testing the feasibility of plerixafor (PLX) in combination with R-DHAP and G-CSF in 37 patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) in order to collect a large number of HSC with a goal of transplantation. After R-DHAP, daily monitoring of peripheral blood CD34 + cells by flow cytometry was performed starting on day + 13.
View Article and Find Full Text PDFMolecular regulators of chemotaxis in human hematopoietic stem cells.
Biochem Soc Trans
December 2024
Zhongshan-Xuhui Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Hematopoietic stem cells (HSCs), essential for lifelong blood cell regeneration, are clinically utilized to treat various hematological disorders. These cells originate in the aorta-gonad-mesonephros region, expand in the fetal liver, and mature in the bone marrow. Chemotaxis, involving gradient sensing, polarization, and migration, directs HSCs and is crucial for their homing and mobilization.
View Article and Find Full Text PDFEvidence Supporting Conservative Scar Management Interventions Following Burn Injury: a review article.
J Burn Care Res
November 2024
School of Physical and Occupational Therapy, McGill University, Montréal, Québec, Canada.
Conservative management for hypertrophic scars (HSc) and scar contractures is of utmost importance to optimally reintegrate burn survivors into society. Many conservative treatment interventions have been described in the literature for the management of HSc. Recent advancements in the literature pertaining to post-burn scarring and HSc formation, have advanced our understanding of the mechanisms that support or refute the use of common rehabilitation treatment modalities after burn injury.
View Article and Find Full Text PDFPulse Activation of Retinoic Acid Receptor Enhances Hematopoietic Stem Cell Homing by Controlling CXCR4 Membrane Presentation.
Stem Cell Rev Rep
October 2024
Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and The Shanghai Key Laboratory of Medical Epigenetics, The International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Article Synopsis
- The study investigates how adapalene, a retinoic acid receptor agonist, influences the migration of hematopoietic stem cells (HSCs).
- Adapalene reduces the mobilization of hematopoietic stem and progenitor cells (HSPCs) and increases the surface expression of CXCR4, which enhances their movement towards a specific chemical signal (CXCL12).
- The research suggests a unique function of retinoic acid signaling in HSC behavior, showing that treatment with adapalene improves HSC homing and donor chimerism in transplantation, indicating potential for new therapies.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!