Single-cell transcriptomic reveals molecular diversity and developmental heterogeneity of human stem cell-derived oligodendrocyte lineage cells
| Autor: | Xitiz Chamling, Donald J. Zack, Zhicheng Ji, Itzy E. Morales Pantoja, Aniruddha M. Kaushik, Matthew D. Smith, Prajwal Devkota, Cynthia A. Berlinicke, Tza-Huei Wang, Joseph L. Mertz, Katharine A. Whartenby, Calvin Chang, Hongkai Ji, Weixiang Fang, Peter A. Calabresi, Liben Chen, Alyssa Kallman, Hai-Quan Mao |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Receptor Platelet-Derived Growth Factor alpha Science Induced Pluripotent Stem Cells General Physics and Astronomy Developmental neurogenesis Biology Article General Biochemistry Genetics and Molecular Biology Cell Line Transcriptome Genetic Heterogeneity 03 medical and health sciences 0302 clinical medicine Pluripotent stem cells medicine Humans Cell Lineage Gene Regulatory Networks Remyelination Induced pluripotent stem cell Embryonic Stem Cells PI3K/AKT/mTOR pathway Oligodendrocyte Precursor Cells Multidisciplinary TOR Serine-Threonine Kinases Genetic Variation RNA sequencing Cell Differentiation General Chemistry Oligodendrocyte Embryonic stem cell Cell biology Cholesterol 030104 developmental biology medicine.anatomical_structure Cell culture Astrocytes Single-Cell Analysis Stem cell Astrocyte 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-20 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Injury and loss of oligodendrocytes can cause demyelinating diseases such as multiple sclerosis. To improve our understanding of human oligodendrocyte development, which could facilitate development of remyelination-based treatment strategies, here we describe time-course single-cell-transcriptomic analysis of developing human stem cell-derived oligodendrocyte-lineage-cells (hOLLCs). The study includes hOLLCs derived from both genome engineered embryonic stem cell (ESC) reporter cells containing an Identification-and-Purification tag driven by the endogenous PDGFRα promoter and from unmodified induced pluripotent (iPS) cells. Our analysis uncovers substantial transcriptional heterogeneity of PDGFRα-lineage hOLLCs. We discover sub-populations of human oligodendrocyte progenitor cells (hOPCs) including a potential cytokine-responsive hOPC subset, and identify candidate regulatory genes/networks that define the identity of these sub-populations. Pseudotime trajectory analysis defines developmental pathways of oligodendrocytes vs astrocytes from PDGFRα-expressing hOPCs and predicts differentially expressed genes between the two lineages. In addition, pathway enrichment analysis followed by pharmacological intervention of these pathways confirm that mTOR and cholesterol biosynthesis signaling pathways are involved in maturation of oligodendrocytes from hOPCs. Brain myelinating oligodendrocytes are rare and difficult to isolate, which has limited data on their development. Here the authors develop a reporter for scalable purification of human pluripotent stem cell derived oligodendrocyte lineage cells, and use this to map differentiation using single cell RNA-sequencing |
| Databáze: | OpenAIRE |
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