Hematopoietic stem and progenitor cells as novel prognostic biomarkers of longevity in a murine model for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a difficult diagnosis and prognosis. In this regard, new and more reliable biomarkers for the disease are needed. We propose peripheral blood, and, more specifically, the hematopoietic stem and progenitor cells (HSPCs) as potential prognostic biomarkers in the SOD1G93A murine model of ALS. We accurately and serially studied three HSPCs—hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs)—in both control and SOD1G93A mice along the disease's progression by RT-PCR and flow cytometry analysis. We found interesting differences for every HSPC type in the transgenic mice compared with the control mice at every time point selected, as well as differences along the disease course. The results showed a maintained compensatory increase of HSCs along disease progression. However, the downregulated levels of CLPs and CMPs suggested an exit of these cell populations to the peripheral tissues, probably due to their supporting role to the damaged tissues. In addition, a positive correlation of the percentage of CLPs and CMPs with the longevity was found, as well as a positive correlation of HSCs and CMPs with motor function and weight, thus reinforcing the idea that HSPCs play a relevant role in the longevity of the SOD1G93A mice. On the basis of these results, both CLPs and CMPs could be considered prognostic biomarkers of longevity in this animal model, opening the door to future studies in human patients for their potential clinical use.

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759. Reduction of HLH-like Manifestations in Murine Model of Munc13-4 Deficiency Following Lentiviral Gene Transfer into Hematopoietic Stem and Progenitor Cells

Molecular Therapy ◽

10.1016/s1525-0016(16)33567-5 ◽

2016 ◽

Vol 24 ◽

pp. S300

Author(s):

Tayebeh-Shabi Soheili ◽

Fernando Sepulveda ◽

Amandine Durand ◽

Julie Rivière ◽

Samia Martin ◽

...

Keyword(s):

Gene Transfer ◽

Progenitor Cells ◽

Murine Model ◽

Hematopoietic Stem ◽

Stem And Progenitor Cells

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Postsynaptic Alteration of NR2A Subunit and Defective Autophosphorylation of alphaCaMKII at Threonine-286 Contribute to Abnormal Plasticity and Morphology of Upper Motor Neurons in Presymptomatic SOD1G93A Mice, a Murine Model for Amyotrophic Lateral Sclerosis

Cerebral Cortex ◽

10.1093/cercor/bhq152 ◽

2010 ◽

Vol 21 (4) ◽

pp. 796-805 ◽

Cited By ~ 18

Author(s):

A. Spalloni ◽

N. Origlia ◽

C. Sgobio ◽

A. Trabalza ◽

M. Nutini ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Murine Model ◽

Sod1g93a Mice ◽

Upper Motor Neurons ◽

Nr2a Subunit ◽

Lateral Sclerosis

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Direct Sensing of Toll-Like Receptor Agonists by Dendritic Cell Progenitors Leads to Their Homing to Inflamed Lymph Nodes Via Regulation of CXCR4 and CCR7

Blood ◽

10.1182/blood.v116.21.3895.3895 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3895-3895

Author(s):

Michael A Schmid ◽

Dior Baumjohann ◽

Markus G Manz

Keyword(s):

Bone Marrow ◽

Steady State ◽

Lymph Nodes ◽

Progenitor Cells ◽

Conflicts Of Interest ◽

Lymphoid Tissues ◽

Hematopoietic Stem ◽

Peripheral Tissues ◽

Tlr Agonists ◽

Stem And Progenitor Cells

Abstract Abstract 3895 Dendritic cells (DCs), the key antigen-presenting cell population, continuously need to be regenerated from bone marrow (BM) hematopoietic stem and progenitor cells. Common dendritic progenitors (CDP) were previously shown to efficiently generate DCs in lymphoid and non-lymphoid tissues. How the dissemination of bone marrow (BM) DC-progenitors to peripheral tissues is regulated upon demand remains elusive to date. Acute microbial infections are sensed via Toll-like receptors (TLR). Recent studies showed that stem and progenitor cells express TLRs. We found that CDPs in the BM of mice express relative high levels of Tlr2, Tlr4 and Tlr9, and hypothesized that these might be involved in regulating CDP migration. CDPs in steady-state expressed high levels of Cxcr4, but no, or low Ccr7. Upon direct stimulation with the respective TLR-agonists in vitro, CDPs rapidly down-regulated Cxcr4 and up-regulated Ccr7 mRNA and protein. CDPs that were stimulated with TLR-agonists for only 2 h preferentially homed to the lymph nodes (LN) in expense of BM in steady-state recipients. When TLR-agonists were injected subcutaneously, CDPs gave rise to increased numbers of plasmacytoid DCs, classical DCs, and DCs with a skin-derived migratory phenotype in inflamed LNs on day 4. This was not due to increased proliferative activity. Injecting the CXCR4 antagonist AMD3100 demonstrated that the retention of CDPs in the BM depends on CXCR4. Furthermore, CCR7 was important for the engraftment of CDP-derived DCs into LNs in steady-state and during inflammation. In conclusion, DC progenitors in the bone marrow are capable to directly sense TLR-agonists via their cognate receptors in systemic infections. This results in differential expression of chemokine receptors and consecutive migration of DC-progenitors to inflamed LNs. This mechanism helps to restore DC subsets during ongoing immune responses and to return to DC homeostasis once the inflammation ceases. Disclosures: No relevant conflicts of interest to declare.

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