We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Cooperativity Between Myeloid Lineages Promotes Langerhans Cell Histiocytosis Pathology

By LabMedica International staff writers
Posted on 04 Jan 2023

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia seen in children and adults who present with lesions composed of pathologic variants of myeloid cells that share certain phenotypic features with Langerhans cells normally found in the epidermis. More...

LCH is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu.

An International team of Clinical Pathologists led by the group at the Karolinska Institutet (Stockholm, Sweden) used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. They used cryopreserved lesional cell suspension analysis from recruited pediatric patients with LCH. Cell suspensions from lesions of pediatric patients with LCH were index-sorted on a FACSAria III (BD Biosciences, San Diego, CA, USA).

Among the many methods used by the team were: index sorting and preprocessing, quality assessment and analysis of Smart-seq2 single-cell transcriptome data; trajectory inference and single-cell entropy analysis; gene regulatory network, cell-cell communication, and RNA velocity analysis; analysis of single-cell skin data from database DISCO integrated with LCH data; culture systems, preparation of skin and gut samples, and staining; and immunofluorescent analysis of tissue sections was performed using the MACSima Imaging Platform (Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany), which enables fully automated immunofluorescent labeling and imaging of individual biological samples.

The investigators reported that they had found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. They also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Signaling mediated by the Notch pathway enables these two cellular lineages to cooperatively form LCH lesions.

The authors concluded that their data suggest a dual origin model of LCH cells, linked by Notch-mediated cooperativity, and provide several new insights into the development of LCH lesions and their potential vulnerabilities to new therapeutic approaches. A single-cell dissection of neoplastic histiocytes and their microenvironment allows clear differentiation of functions between lineages, illustrating the potential for a tissue program to be initiated and generated by cross-talk between more than one immune cell type. The study was published on December 16, 2022 in the journal Science Immunology.

Related Links:
Karolinska Institutet
BD Biosciences
Miltenyi Biotec


New
Gold Member
Serological Pipets
INTEGRA Serological Pipets
Serological Pipet Controller
PIPETBOY GENIUS
New
PSA Assay
CanAg PSA EIA
New
Automated Biochemical Analyzer
iBC 900
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








DIASOURCE (A Biovendor Company)

Channels

Hematology

view channel
Image: CitoCBC is the world first cartridge-based CBC to be granted CLIA Waived status by FDA (Photo courtesy of CytoChip)

Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results

Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more

Pathology

view channel
These images illustrate how precision oncology Organ Chips recapitulate individual patients’ responses to chemotherapy (Photo courtesy of Wyss Institute at Harvard University)

Cancer Chip Accurately Predicts Patient-Specific Chemotherapy Response

Esophageal adenocarcinoma (EAC), one of the two primary types of esophageal cancer, ranks as the sixth leading cause of cancer-related deaths worldwide and currently lacks effective targeted therapies.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.