PB0384 - Spatiotemporal evolution of mammalian megakaryocytes during ontogeny

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Cuicui Liu, PhD (she/her/hers)

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

Co-Author(s)

MX

Meijuan Xia

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

Jinjing Zhao

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

Yezi Ma

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

Minmin Li

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

Pei Su

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

Hongtao Wang

associate professor
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and 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: Recent advances in single-cell RNA sequencing (scRNA-seq) technology have revolutionized our understanding of the molecular characteristics and heterogeneity of megakaryocytes (MKs). However, the previous studies mainly focused on limited organs at a specific developmental stage rather than a transcriptomic atlas of MKs across different organs during ontogeny. Thus, it is still unknown how the molecular characteristics and heterogeneity of MKs evolve during ontogenesis.

Aims: This study plans to explore the spatiotemporal evolution of molecular characteristics and heterogeneity of MKs as well as their potential effects to thrombopoiesis.

Methods: The spatiotemporal molecular characteristics and heterogeneity of MKs during mouse ontogenesis were deciphered using scRNA-seq. The ontogenic transition of thrombopoiesis was explored by using mitochondrial fluorescent tracing mice and transplantation model.

Results: We constructed the spatiotemporal molecular atlas of MKs by profiling over 5,000 MKs from seven main resident organs during mouse ontogenesis with scRNA-seq and compare them very carefully. We uncovered that MKs from different organs displayed distinct transcriptional signatures. Furthermore, differences in the heterogeneity of MKs across different organs and their developmental alterations in each organ were revealed. Our results demonstrated the local environment of the organ might play important roles to the development of MKs. More importantly, we identified two MK subpopulations with different thrombopoiesis potential, CD150 high mtRNA low MKs with lower platelet production capacity that mainly existed in the prenatal stage. In contrast, CD150 high mtRNA high MKs with more potent thrombopoiesis capacity gradually predominates after birth.

Conclusion(s): We constructed the spatiotemporal molecular atlas of MKs and revealed the evolutionary process of molecular characteristics, heterogeneity and thrombopoiesis of MKs during ontogenesis, which provides valuable resources and insights into the understanding of the functional diversity of mammalian megakaryocytes as well as how they are developed. It also shed light on future platelet regeneration and clinical applications.