Dissecting the Global Dynamic Molecular Profiles of Human Fetal Kidney Development by Single-Cell RNA Sequencing.

Ping Wang, Yidong Chen, Jun Yong, Yueli Cui, Rui Wang, Lu Wen, Jie Qiao, Fuchou Tang
Author Information
  1. Ping Wang: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
  2. Yidong Chen: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
  3. Jun Yong: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
  4. Yueli Cui: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
  5. Rui Wang: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
  6. Lu Wen: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
  7. Jie Qiao: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, 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. Electronic address: jie.qiao@263.net.
  8. Fuchou Tang: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Science, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. Electronic address: tangfuchou@pku.edu.cn.

Abstract

Healthy renal function depends on normal nephrogenesis during embryonic development. However, a comprehensive gene expression profile of human fetal kidney development remains largely unexplored. Here, using a single-cell RNA-sequencing technique, we analyzed >3,000 human fetal renal cells spanning 4 months of development in utero. Unsupervised analysis identified two progenitor subtypes during cap mesenchyme development, suggesting a mechanism for sustaining their progenitor states. Furthermore, we identified critical transcriptional regulators and signaling pathways involved in the segmentation of nephron tubules. We explored the development of the highly heterogeneous collecting duct epithelia and dissected the metabolic gene repertoire and the extracellular matrix composition of the glomerular mesangium. The results provide insights on the molecular basis and regulatory events in human renal development. Moreover, the cell-type-specific expression features of causal genes in congenital renal diseases may be helpful in the treatment of these diseases.

Keywords

MeSH Term

Gene Expression Profiling
Gene Expression Regulation, Developmental
Humans
Kidney
Single-Cell Analysis
Transcriptome