Clonal analysis of hematopoietic stem and progenitor biology in situ

造血干细胞和祖细胞生物学原位克隆分析

基本信息

  • 批准号:
    9225236
  • 负责人:
  • 金额:
    $ 52.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-02-15 至 2020-01-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Current dogma suggests that all hematolymphoid lineages are derived from a common ancestor, the hematopoietic stem cell (HSC). HSCs are believed to be the only cells with long-term self-renewal capacity in the bone marrow (BM), and are generally regarded as the cell of origin for continuous multi-lineage blood production during adult life. Evidence supporting this HSC-centric paradigm has been acquired through decades of work based largely on the use of functional assays involving transplantation. However, it is unclear to what extent functional characteristics of cells assayed under transplantation conditions are shared with cells driving non-transplant native hematopoiesis. Because of a historical lack of tractable systems, the mechanistic nature of non-transplant blood production has remained largely unexplored. To address this limitation, my laboratory has developed a novel experimental system in mice where cells can be uniquely and genetically labeled in situ. Using this system, clonal fate of multiple hematopoietic populations can be tracked over time and across lineages, for the first time, in a native context. Our preliminary findings with this model have revealed surprisingly unique features of unperturbed hematopoiesis. Among other things, our data demonstrate that long-term native hematopoiesis is mainly driven by waves of progenitor recruitment and that HSC contribution during this process is minimal. Thus, we hypothesize that native hematopoiesis is driven by fundamentally different mechanisms as transplantation. In this proposal, we aim to extend our earlier findings and to provide comprehensive insight into the biology of blood production in situ. Specifically, we will test whether HSCs can be recruited into productive hematopoiesis via injury, stress, or infection. We will also test whether progenitor recruitment can exhaust during the aging process. Additionally, we will revisit the existence of classical progenitor populations and lineage relationships using our clonal strategy. Completion of this project would elucidate the basic mechanisms underlying blood production and provide insight into stem cell dynamics during disease processes.


项目成果

期刊论文数量(0)
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专利数量(0)

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Fernando Camargo其他文献

Fernando Camargo的其他文献

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{{ truncateString('Fernando Camargo', 18)}}的其他基金

High resolution lineage tracing of developmental hematopoiesis
发育造血的高分辨率谱系追踪
  • 批准号:
    10585400
  • 财政年份:
    2023
  • 资助金额:
    $ 52.43万
  • 项目类别:
Generation of a temporal, spatial, and molecular map of in situ hematopoiesis
生成原位造血的时间、空间和分子图
  • 批准号:
    10415468
  • 财政年份:
    2022
  • 资助金额:
    $ 52.43万
  • 项目类别:
Image guided profiling of the native HSC niche
原生 HSC 利基的图像引导分析
  • 批准号:
    10212380
  • 财政年份:
    2019
  • 资助金额:
    $ 52.43万
  • 项目类别:
Image guided profiling of the native HSC niche
原生 HSC 利基的图像引导分析
  • 批准号:
    10018892
  • 财政年份:
    2019
  • 资助金额:
    $ 52.43万
  • 项目类别:
Project 1 - Molecular and cellular determinants of hematopoietic clonal expansion
项目 1 - 造血克隆扩增的分子和细胞决定因素
  • 批准号:
    10641540
  • 财政年份:
    2017
  • 资助金额:
    $ 52.43万
  • 项目类别:
Molecular regulation of native hematopoiesis
天然造血的分子调控
  • 批准号:
    10541825
  • 财政年份:
    2016
  • 资助金额:
    $ 52.43万
  • 项目类别:
Molecular regulation of native hematopoiesis
天然造血的分子调控
  • 批准号:
    10157107
  • 财政年份:
    2016
  • 资助金额:
    $ 52.43万
  • 项目类别:
Molecular regulation of native hematopoiesis
天然造血的分子调控
  • 批准号:
    10321680
  • 财政年份:
    2016
  • 资助金额:
    $ 52.43万
  • 项目类别:
Clonal analysis of hematopoietic stem and progenitor biology in situ
造血干细胞和祖细胞生物学原位克隆分析
  • 批准号:
    9030319
  • 财政年份:
    2016
  • 资助金额:
    $ 52.43万
  • 项目类别:
Reprogramming of liver cell fate by Hippo signaling
通过 Hippo 信号重新编程肝细胞命运
  • 批准号:
    8676791
  • 财政年份:
    2013
  • 资助金额:
    $ 52.43万
  • 项目类别:

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