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| Status |
Public on Feb 15, 2017 |
| Title |
Central nervous system muscarinic receptor type-1 primes HSC mobilization from bone marrow via glucocorticoid-mediated relay |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Here we show that muscarinic type-1 (Chrm1) signaling in the central nervous system (CNS) promotes G-CSF-elicited HSC migration from the BM. Blockade of Chrm1 in the CNS, but not the periphery, reduced HSC mobilization. In Chrm1−⁄− mice, reduced mobilization was rescued by wild-type parabionts, suggesting the contribution of a soluble factor. We found that corticosterone levels were dramatically reduced in the BM, and its exogenous administration normalized the mobilization deficit of Chrm1−⁄− animals. Chrm1−⁄− HSCs have reduced nuclear glucocorticoid receptors (Nr3c1) and alterations in the expression of actin-organizing molecules. Polymerized actin formation and HSC mobilization are also impaired in mice harboring Nr3c1-deficient hematopoietic cells.
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| Overall design |
RNA for microarray analysis was isolated by sorting HSC (Lineage-Sca1+cKit+Flt3- directly into RLT buffer from the RNeasy Plus Micro kit (Qiagen) according to the manufacturer’s instructions. Amplification and subsequent microarray was performed by the Genomics Core Facility at Albert Einstein College of Medicine using the One-Direct RNA amplification system (NuGEN) and GeneChip mouse gene 2.0 ST array (Affymetrix). Analysis was performed by first processing the chip through Transcriptome analysis center (TAC) software (Affymetrix) to determine fold changes and p-values which were then analyzed by gene set enrichment analysis (GSEA).
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| Contributor(s) |
Pierce H, Magnon C, Lucas D, Huggins M, Schwartz GJ, Frenette PS |
| Citation(s) |
28196601 |
| |
| Submission date |
Dec 27, 2015 |
| Last update date |
Aug 29, 2019 |
| Contact name |
Halley C Pierce |
| E-mail(s) |
halley.c.ketchum@phd.einstein.yu.edu
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| Organization name |
Albert Einstein College of Medicine
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| Department |
Ruth L. and David S. Gottesman Stem Cell Institutue
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| Lab |
Paul Frenette
|
| Street address |
1301 Morris Park Ave.
|
| City |
Bronx |
| State/province |
NY |
| ZIP/Postal code |
10461 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA307066 |
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