Growth factor dependency in mammary organoids regulates ductal morphogenesis during organ regeneration.
Growth factor dependency in mammary organoids regulates ductal morphogenesis during organ regeneration.
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乳腺类器官中的生长因子依赖性调节器官再生期间的导管形态发生。
DOI：
10.1038/s41598-022-11224-6
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发表时间：
2022-05-03
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
信号通路在干细胞的细胞命运决定中起着重要作用，并调节过多的发育程序，其失调可导致人类疾病。因此，调节这些信号通路的生长因子（GF）在成体干细胞的可塑性中起着重要作用，并调节细胞分化和组织修复结果。我们认为小鼠乳腺类器官的生成自组织成体干细胞作为一种工具，以了解在器官发育和组织再生的GF的作用。乳腺类器官在移植后体内再生腺体的惊人能力使其成为研究器官再生的方便模型。我们显示在具有最小浓度的基质胶的悬浮液中生长的类器官，并且在调节EGF和FGF信号传导的GF的混合物的存在下，可以重现成年乳腺的关键上皮层。我们建立了一个工具包，利用在体内整个动物成像和超声成像结合离体方法，包括组织清除和共聚焦成像研究器官再生和导管形态发生。虽然类器官的结构在体外培养时，在个别GF的存在下严重受损，离体成像显示导管分支移植后，虽然有显着减少的终端芽的数量。我们预计这些成像方式将开辟新的途径，研究乳腺形态发生在体内，并可能有利于监测乳腺肿瘤的进展，在临床前和临床设置。
Signaling pathways play an important role in cell fate determination in stem cells and regulate a plethora of developmental programs, the dysregulation of which can lead to human diseases. Growth factors (GFs) regulating these signaling pathways therefore play a major role in the plasticity of adult stem cells and modulate cellular differentiation and tissue repair outcomes. We consider murine mammary organoid generation from self-organizing adult stem cells as a tool to understand the role of GFs in organ development and tissue regeneration. The astounding capacity of mammary organoids to regenerate a gland in vivo after transplantation makes it a convenient model to study organ regeneration. We show organoids grown in suspension with minimal concentration of Matrigel and in the presence of a cocktail of GFs regulating EGF and FGF signaling can recapitulate key epithelial layers of adult mammary gland. We establish a toolkit utilizing in vivo whole animal imaging and ultrasound imaging combined with ex vivo approaches including tissue clearing and confocal imaging to study organ regeneration and ductal morphogenesis. Although the organoid structures were severely impaired in vitro when cultured in the presence of individual GFs, ex vivo imaging revealed ductal branching after transplantation albeit with significantly reduced number of terminal end buds. We anticipate these imaging modalities will open novel avenues to study mammary gland morphogenesis in vivo and can be beneficial for monitoring mammary tumor progression in pre-clinical and clinical settings.
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R-spondin1 是一种用于乳腺干细胞自我更新的新型激素介质
影响因子：
10.5
作者：
Cai C;Yu QC;Jiang W;Liu W;Song W;Yu H;Zhang L;Yang Y;Zeng YA
通讯作者：
Zeng YA
影响因子：
64.5
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
通讯作者：
Ewald AJ
影响因子：
14.8
作者：
Dekkers, Johanna F.;Alieva, Maria;Rios, Anne C.
通讯作者：
Rios, Anne C.
影响因子：
48
作者：
Duarte, Alexandra A.;Gogola, Ewa;Rottenberg, Sven
通讯作者：
Rottenberg, Sven
DOI：
10.1073/pnas.1715272116
发表时间：
2019-07-16
影响因子：
11.1
作者：
Boonekamp, Kim E.;Kretzschmar, Kai;Clevers, Hans
通讯作者：
Clevers, Hans