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Skull and vertebral bone marrow are myeloid reservoirs for meninges and CNS parenchyma

ABSTRACT: Skull and vertebral bone marrow are myeloid reservoirs for meninges and CNS parenchyma

PROVIDER: PRJNA675284 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14249186_1.fastq.gz	Fastqsanger.gz
	SRR14249186_2.fastq.gz	Fastqsanger.gz
	SRR14249187_1.fastq.gz	Fastqsanger.gz
	SRR14249187_2.fastq.gz	Fastqsanger.gz
	SRR14249188_1.fastq.gz	Fastqsanger.gz

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Skull and vertebral bone marrow are myeloid reservoirs for meninges and CNS parenchyma

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Cranial photo-immunologic regulation along the skull-meninges-brain axis for promoting recovery from ischemic brain injury

Project description:Stroke involves in the interaction between central and peripheral immune systems. Skull bone marrows serve as reservoirs for immune cells in brain borders, and can rapidly respond to perturbations in the brain environment. Hence, targeting the skull bone marrow to modulate neuroimmune communications along the calvaria-meninges-brain axis would potentially improve stroke prognosis. Here, we successfully achieved cranial immunomodulation via ultraviolet (UV) irradiation of the interparietal region, which was characterized by rich marrow cavities and channels connecting the skull and meninges. Utilizing the recently-developed long-term clearing cranial window that ensured the integrity of skull, we discovered that the cranial photo-immunologic regulation (CPR) could promote cerebrovascular regeneration and aid in neurovascular repair post ischemic stroke. Single-cell transcriptome analysis revealed that meninge could be a crucial neuroimmune interface for ischemic stroke-induced immune responses. And, CPR could restore the stroke-induced alterations in cellular gene expression, especially meningeal B cells. Further we demonstrated that CPR could effectively alleviate the excessive suppression of meningeal B cell activation caused by ischemic stroke. This work opens avenues for immunoregulation through the skull-meninges-brain axis and provides valuable insights for immunomodulatory therapies in brain diseases.

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Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma.

Project description:The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the mouse meninges contain a pool of monocytes and neutrophils supplied not from the blood but by adjacent skull and vertebral bone marrow. Under pathological conditions, including spinal cord injury and neuroinflammation, CNS-infiltrating myeloid cells can originate from brain borders and display transcriptional signatures distinct from their blood-derived counterparts. Thus, CNS borders are populated by myeloid cells from adjacent bone marrow niches, strategically placed to supply innate immune cells under homeostatic and pathological conditions. These findings call for a reinterpretation of immune-cell infiltration into the CNS during injury and autoimmunity and may inform future therapeutic approaches that harness meningeal immune cells.

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