Functional interrogation of a novel SCGB3A2+/SFTPB+ cell in the human airway
人类气道中新型 SCGB3A2 /SFTPB 细胞的功能询问
基本信息
- 批准号:10555804
- 负责人:
- 金额:$ 58.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:ASCL1 geneAtlasesBar CodesBasal CellBiologyCell Differentiation processCell LineageCell surfaceCellsConceptionsCystic Fibrosis Transmembrane Conductance RegulatorDataEpithelial CellsEpitheliumGene Expression ProfileGenesGoalsHumanIn VitroLungMADH2 geneMediatingMethodsModelingMusNeuroendocrine CellOrganoidsPhasePopulationPublishingReportingSecretory CellSignal TransductionSystemTestingTime Series AnalysisTissuescell typeexperimental studyfetalfollow-upgenetic signaturein vitro Modelinhibitorinsightnovelpharmacologicprogenitorsingle-cell RNA sequencingstem cellstool
项目摘要
ABSTRACT
During a recent single cell RNA sequencing analysis of the developing human lung, we identified a cell
population characterized by a unique gene expression profile that has not previously been reported in the
human or mouse lung. These cells express SCGB3A2/SFTPB/CFTR, but lack markers for other well
characterized cell types such as club cells (SCGB1A1) or ionocytes (FOXI1). We refer to these as Fetal Airway
Secretory (FAS) cells given the expression of several secretory genes within the transcriptional signature.
Since nothing is known about FAS cells, and there is no analogous population in the murine lung, the
overarching goal of this proposal is to both describe these cells in detail, to interrogate their differentiation
potential, and to determine how these cells are regulated. By using an in vitro model of the developing human
lung epithelium called human Bud Tip Progenitor (BTP)-organoids, preliminary data shows that BTP-organoids
can give rise to both TP63+ progenitors and FAS cells during airway differentiation, and that this differentiation
can be modulated by TGFb/BMP/SMAD signaling. Single cell barcode-based lineage tracing during the
transition from BTP-to-airway suggest that clones of FAS cells or basal cells give rise to distinct subsets of
airway cells, with FAS cells giving rise to pulmonary neuroendocrine cells (PNECs) and a subset of C6+
multiciliated (MC) cells, while TP63+ progenitor cells give rise to secretory cells and MUC16+ MC cells. Based
on this data, we will test the overarching hypothesis that FAS cells differentiate distinct airway progenitor cell
that give rise to a subset of airway cell types. Given the novelty of this cell type, and the unique tools that we
have developed to assess the differentiating human epithelium in vitro, understanding this cell population will
provide foundational descriptive and mechanistic insights into human lung biology.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Jason Spence其他文献
Jason Spence的其他文献
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{{ truncateString('Jason Spence', 18)}}的其他基金
Engineered human intestinal organoids: a modular system to model enteric disease
工程人体肠道类器官:模拟肠道疾病的模块化系统
- 批准号:
9240575 - 财政年份:2015
- 资助金额:
$ 58.22万 - 项目类别:
Mechanisms of fetal intestinal stem cell regulation and maturation
胎儿肠道干细胞调节和成熟的机制
- 批准号:
9334833 - 财政年份:2014
- 资助金额:
$ 58.22万 - 项目类别:
Mechanisms of fetal intestinal stem cell regulation and maturation
胎儿肠道干细胞调节和成熟的机制
- 批准号:
8918614 - 财政年份:2014
- 资助金额:
$ 58.22万 - 项目类别:
Mechanisms of fetal intestinal stem cell regulation and maturation
胎儿肠道干细胞调节和成熟的机制
- 批准号:
9130821 - 财政年份:2014
- 资助金额:
$ 58.22万 - 项目类别:
Mechanisms of fetal intestinal stem cell regulation and maturation
胎儿肠道干细胞调节和成熟的机制
- 批准号:
8774401 - 财政年份:2014
- 资助金额:
$ 58.22万 - 项目类别:
Mechanisms of fetal intestinal stem cell regulation and maturation
胎儿肠道干细胞调节和成熟的机制
- 批准号:
9135766 - 财政年份:2014
- 资助金额:
$ 58.22万 - 项目类别:
Control of progenitor cell maintenance and differentiation in the developing lung
控制发育中的肺中祖细胞的维持和分化
- 批准号:
10181016 - 财政年份:2013
- 资助金额:
$ 58.22万 - 项目类别:
A Hox-Wnt-Sox signaling axis regulates lung development, patterning and branching
Hox-Wnt-Sox 信号轴调节肺发育、模式和分支
- 批准号:
9069987 - 财政年份:2013
- 资助金额:
$ 58.22万 - 项目类别:
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