A human fetal cerebellar map of the late second trimester reveals developmental molecular characteristics and abnormality in trisomy 21
Hongmin Yu,
Yun Liu,
Fanqing Xu,
Yuanyuan Fu,
Ming Yang,
Ling Ding,
Yixuan Wu,
Fuchou Tang,
Jie Qiao,
Lu Wen
Affiliations
Hongmin Yu
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China
Yun Liu
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Changping Laboratory, Changping Laboratory, Yard 28, Science Park Road, Changping District, Beijing 102206, China
Fanqing Xu
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
Yuanyuan Fu
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China
Ming Yang
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
Ling Ding
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
Yixuan Wu
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
Fuchou Tang
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Changping Laboratory, Changping Laboratory, Yard 28, Science Park Road, Changping District, Beijing 102206, China
Jie Qiao
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China; Corresponding author
Lu Wen
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Changping Laboratory, Changping Laboratory, Yard 28, Science Park Road, Changping District, Beijing 102206, China; Corresponding author
Summary: Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18–25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.
