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单细胞转录组谱分析小鼠和 hESC 来源的胰腺祖细胞。

Single-Cell Transcriptome Profiling of Mouse and hESC-Derived Pancreatic Progenitors.

机构信息

Diabetes Research Group, BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada; Departments of Surgery and Cellular and Physiological Sciences, University of British Columbia, 950 28(th) Avenue West, Vancouver, BC V5Z4H4, Canada.

Diabetes Research Group, BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada.

出版信息

Stem Cell Reports. 2018 Dec 11;11(6):1551-1564. doi: 10.1016/j.stemcr.2018.11.008.

DOI:10.1016/j.stemcr.2018.11.008
PMID:30540962
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6294286/
Abstract

Human embryonic stem cells (hESCs) are a potential unlimited source of insulin-producing β cells for diabetes treatment. A greater understanding of how β cells form during embryonic development will improve current hESC differentiation protocols. All pancreatic endocrine cells, including β cells, are derived from Neurog3-expressing endocrine progenitors. This study characterizes the single-cell transcriptomes of 6,905 mouse embryonic day (E) 15.5 and 6,626 E18.5 pancreatic cells isolated from Neurog3-Cre; Rosa26 embryos, allowing for enrichment of endocrine progenitors (yellow; tdTomato + EGFP) and endocrine cells (green; EGFP). Using a NEUROG3-2A-eGFP CyT49 hESC reporter line (N5-5), 4,462 hESC-derived GFP+ cells were sequenced. Differential expression analysis revealed enrichment of markers that are consistent with progenitor, endocrine, or previously undescribed cell-state populations. This study characterizes the single-cell transcriptomes of mouse and hESC-derived endocrine progenitors and serves as a resource (https://lynnlab.shinyapps.io/embryonic_pancreas) for improving the formation of functional β-like cells from hESCs.

摘要

人类胚胎干细胞（hESC）是治疗糖尿病的胰岛素产生β细胞的潜在无限来源。更好地了解胚胎发育过程中β细胞的形成方式将改进当前的 hESC 分化方案。所有胰腺内分泌细胞，包括β细胞，均源自表达 Neurog3 的内分泌祖细胞。本研究对来自 Neurog3-Cre；Rosa26 胚胎的 6905 个 E15.5 日龄和 6626 个 E18.5 日龄的胰腺细胞的单细胞转录组进行了特征分析，可富集内分泌祖细胞（黄色；tdTomato+EGFP）和内分泌细胞（绿色；EGFP）。使用 NEUROG3-2A-eGFP CyT49 hESC 报告基因系（N5-5），对 4462 个 hESC 来源的 GFP+细胞进行了测序。差异表达分析显示，与祖细胞、内分泌细胞或以前未描述的细胞状态群体一致的标记物富集。本研究对小鼠和 hESC 来源的内分泌祖细胞的单细胞转录组进行了特征分析，并作为资源（https://lynnlab.shinyapps.io/embryonic_pancreas），用于提高 hESC 功能性β样细胞的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/0eca9ef098d3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/74738856070b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/68de5213080a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/49c0a57822d9/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/7e1cef560df6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/a5fcdd3dd0a2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/de7dd52f503d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/0eca9ef098d3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/74738856070b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/68de5213080a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/49c0a57822d9/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/7e1cef560df6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/a5fcdd3dd0a2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/de7dd52f503d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b63/6294286/0eca9ef098d3/gr6.jpg

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