scholarly journals Engrafted parenchymal brain macrophages differ from host microglia in transcriptome, epigenome and response to challenge

2018 ◽  
Author(s):  
Anat Shemer ◽  
Jonathan Grozovski ◽  
Tuan Leng Tay ◽  
Jenhan Tao ◽  
Alon Volaski ◽  
...  
Keyword(s):  
Yolk Sac ◽  
Clinical Settings ◽  
Transplant Recipients ◽  
Brain Macrophages ◽  
Hematopoietic Stem ◽  
Endotoxin Challenge ◽  
Discrete Responses ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Brain Macrophage

AbstractMicroglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. Following different conditioning paradigms and bone marrow (BM) / hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that these cells acquire over time microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even following prolonged CNS residence, transcriptomes and epigenomes of engrafted HSC-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, BM graft-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. Also in human HSC transplant recipients, engrafted cells remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for patients treated by HSC gene therapy.

scholarly journals Comparative analysis of CreER transgenic mice for the study of brain macrophages – a case study

2019 ◽  
Author(s):  
Louise Chappell-Maor ◽  
Masha Kolesnikov ◽  
Jonathan Grozovski ◽  
Jung-Seok Kim ◽  
Anat Shemer ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cre Recombinase ◽  
Brain Macrophages ◽  
Technological Advances ◽  
Communication Circuits ◽  
Cell Type Specific ◽  
Definition Of ◽  
The Brain ◽  
Brain Macrophage

AbstractConditional mutagenesis and fate mapping have contributed considerably to our understanding of physiology and pathology. Specifically, Cre recombinase-based approaches allow the definition of cell type-specific contributions to disease development and inter-cellular communication circuits in respective animals models. Here we compared Cx3cr1CreER and Sall1CreER transgenic mice and their use to decipher the brain macrophage compartment as a showcase to discuss recent technological advances. Specifically, we highlight the need to define the accuracy of Cre recombinase expression, as well as strengths and pitfalls of these particular systems that should be taken into consideration when applying these models.

scholarly journals Engraftment of Embryonic Hematopoietic Cells in Conditioned Newborn Recipients

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2176-2183 ◽  
Author(s):  
Mervin C. Yoder ◽  
Kelly Hiatt
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Hematopoietic Cells ◽  
Yolk Sac ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Normal Peripheral Blood ◽  
Cell Counts ◽  
Adult Recipient ◽  
Yolk Sac Cells

Abstract Yolk sac hematopoiesis is characterized by restricted hematopoietic cell differentiation. Although multipotent hematopoietic progenitor cells have been identified in the early yolk sac, long-term multilineage repopulating (LTMR) hematopoietic stem cell (HSC) activity has not been demonstrable before day 11 postcoitus (PC) using standard transplantation assays. In the present study, day-10 PC yolk sac hematopoietic cells were infused into myeloablated congenic newborn pups and donor cell engraftment and multilineage reconstitution of peripheral blood cells for at least 11 months in primary recipients was observed. In contrast, transplantation of day-10 PC yolk sac cells into congenic adult recipients did not result in engraftment despite pretransplant conditioning of the recipients or use of recipients that were genetically deficient in stem cells. Although fresh yolk sac cells were incapable of reconstitution when injected into adult recipient mice, yolk sac donor-derived cells residing in the bone marrow of primary newborn transplant recipients were capable of efficient reconstitution of conditioned secondary recipient adult mice. Primary newborn and secondary adult recipient animals engrafted with yolk sac cells were observed to have normal peripheral blood white blood cell counts. Lymphocyte subsets in peripheral blood, thymus, and spleen were also similar to control animals. The distribution and frequency of lineage-restricted progenitors derived from bone marrow of secondary transplant recipients were normal. These results indicate that day-10 PC yolk sac HSCs are capable of engrafting and reconstituting the hematopoietic system of conditioned newborn but not adult recipient animals. Furthermore, the ability of the yolk sac HSCs to differentiate into all hematopoietic lineages in these recipients strongly suggests that the local cellular microenvironment plays a prominent role in regulating yolk sac HSC differentiation.

scholarly journals Tissue-Resident Macrophage Development and Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Yinyu Wu ◽  
Karen K. Hirschi
Keyword(s):  
Fetal Liver ◽  
Yolk Sac ◽  
Adult Brain ◽  
Third Wave ◽  
Biological Processes ◽  
Hematopoietic Stem ◽  
Primitive Hematopoiesis ◽  
And Function ◽  
Second Wave ◽  
The Brain

Tissue-resident macrophages have been associated with important and diverse biological processes such as native immunity, tissue homeostasis and angiogenesis during development and postnatally. Thus, it is critical to understand the origins and functions of tissue-resident macrophages, as well as mechanisms underlying their regulation. It is now well accepted that murine macrophages are produced during three consecutive waves of hematopoietic development. The first wave of macrophage formation takes place during primitive hematopoiesis, which occurs in the yolk sac, and gives rise to primitive erythroid, megakaryocyte and macrophage progenitors. These “primitive” macrophage progenitors ultimately give rise to microglia in the adult brain. The second wave, which also occurs in the yolk sac, generates multipotent erythro-myeloid progenitors (EMP), which give rise to tissue-resident macrophages. Tissue-resident macrophages derived from EMP reside in diverse niches of different tissues except the brain, and demonstrate tissue-specific functions therein. The third wave of macrophages derives from hematopoietic stem cells (HSC) that are formed in the aorta-gonad-mesonephros (AGM) region of the embryo and migrate to, and colonize, the fetal liver. These HSC-derived macrophages are a long-lived pool that will last throughout adulthood. In this review, we discuss the developmental origins of tissue-resident macrophages, their molecular regulation in specific tissues, and their impact on embryonic development and postnatal homeostasis.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

Pelvic schwannoma

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. 84-86
Author(s):  
Sergei P. Sinchikhin ◽  
Sarkis G. Magakyan ◽  
Oganes G. Magakyan
Keyword(s):  
Auditory Nerve ◽  
World Literature ◽  
Morphological Study ◽  
Clinical Observation ◽  
Nerve Trunk ◽  
Practical Case ◽  
Surgical Volume ◽  
The World ◽  
Brain And Spinal Cord ◽  
The Brain

Relevance.A neoplasm originated from the myelonic sheath of the nerve trunk is called neurinoma or neurilemmoma, neurinoma, schwannoglioma, schwannoma. This tumor can cause compression and dysfunction of adjacent tissues and organs. The most common are the auditory nerve neurinomas (1 case per 100 000 population per year), the brain and spinal cord neurinomas are rare. In the world literature, there is no information on the occurrences of this tumor in the pelvic region. Description.Presented below is a clinical observation of a 30-year-old patient who was scheduled for myomectomy. During laparoscopy, an unusual tumor of the small pelvis was found and radically removed. A morphological study allowed to identify the remote neoplasm as a neuroma. Conclusion.The presented practical case shows that any tumor can hide under a clinical mask of another disease. The qualification of the doctor performing laparoscopic myomectomy should be sufficient to carry out, if necessary, another surgical volume.

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