PB0725 - Novel Resident Sites, Organ and Stage-Associated Diversity of Mammalian Megakaryocytes

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Meijuan Xia, PhD

Post-Doctor
Institute of Hematology&Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, Tianjin, China (People's Republic)

Co-Author(s)

CL

Cuicui Liu

Research assistant
Institute of Hematology, Blood Disease Hospital,Chinese Academy of Medical Science (CAMS)
Tianjin, Tianjin, China (People's Republic)
YM

Yezi Ma

Student
Institute of Hematology, Blood Disease Hospital,Chinese Academy of Medical Science (CAMS)
Tianjin, Tianjin, China (People's Republic)
JZ

Jingjing Zhao

Research assistant
Institute of Hematology, Blood Disease Hospital,Chinese Academy of Medical Science (CAMS)
Tianjin, Tianjin, China (People's Republic)
HW

Hongtao Wang

Research Associate Professor
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, Tianjin, China (People's Republic)
Jiaxi Zhou, Ph.D

professor
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tianjin, Tianjin, China (People's Republic)

Background: Megakaryocytes (MKs) appear to arise from diverse organs and stages, implying multi-organ, multi-stage distribution. However, uncertainty remains about other MK-resident organs and the reasons for their presence in different developmental stages and organs.

Aims: We aim to find the previously uncharted MK-reservoir organs and discover organ-specific molecular traits and functional diversity of MKs.

Methods: The single-cell transcriptomics from MKs spanning six known resident organs were performed to uncovering distinct molecular signature of each organ’s MK population. The MK identification system (MKIDS) was discovered through machine learning to identify MKs in uncharted reservoir organs, using this dataset of MKs. The integrative analysis of MKs from multi-organ and multi-stage was conducted to explore the spatiotemporal evolution of molecular characteristics and heterogeneity of MKs as well as their potential effects to thrombopoiesis.

Results: We constructed the spatiotemporal molecular atlas of MKs, discovered new MK markers and established MKIDS, outperforming traditional methods in sensitivity and specificity. By employing MKIDS, we identified MKs in nine uncharted reservoir organs including brain, heart, and placenta. Notably, brain MKs exhibited unique molecular features associated with neurodevelopment and interactions with various brain cells. Thereafter, we revealed seven MK subpopulations that displayed dynamic transitions, with an embryonic-specific brain niche subpopulation and a mitochondria-rich adult bone marrow subpopulation responsible for platelet production.

Conclusion(s): We have newly created a MKIDS that is well applied to the discovery of MKs in different organs; We found that MKs are present in many uncharted reservoir organs and discovered the unique neurodevelopment-supporting molecular features of brain MKs; We revealed the diversity of MKs heterogeneity as well as their spatiotemporal evolution and identified a new mitochondria-rich MK subpopulation responsible for platelet production in adult bone marrow. This study transforms our understanding of MKs, shedding light on their functional diversity and platelet generation processes.