Cell Stem Cell
Abstract
The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax+ hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1+ and Neurog2+ IPCs. Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity.
| 论文编号: | DOI:10.1016/j.stem.2021.03.020 |
| 论文题目: | Cascade Diversification Directs Generation of Neuronal Diversity in the Hypothalamus |
| 英文论文题目: | Cascade Diversification Directs Generation of Neuronal Diversity in the Hypothalamus |
| 第一作者: | Yuhong Zhang, Mingrui Xu, Xiang Shi, Xue-Lian Sun, Wenhui Mu, Haoda Wu, Jingjing Wang, Si Li, Pengfei Su, Ling Gong, Miao He, Mingze Yao and Qingfeng Wu |
| 英文第一作者: | Yuhong Zhang, Mingrui Xu, Xiang Shi, Xue-Lian Sun, Wenhui Mu, Haoda Wu, Jingjing Wang, Si Li, Pengfei Su, Ling Gong, Miao He, Mingze Yao and Qingfeng Wu |
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| 发表年度: | 2021-04-25 |
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| 摘要: | The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax+ hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1+ and Neurog2+ IPCs. Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity. |
| 英文摘要: | The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax+ hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1+ and Neurog2+ IPCs. Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity. |
| 刊物名称: | Cell Stem Cell |
| 英文刊物名称: | Cell Stem Cell |
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| 其它备注: | Yuhong Zhang, Mingrui Xu, Xiang Shi, Xue-Lian Sun, Wenhui Mu, Haoda Wu, Jingjing Wang, Si Li, Pengfei Su, Ling Gong, Miao He, Mingze Yao and Qingfeng Wu. Cascade Diversification Directs Generation of Neuronal Diversity in the Hypothalamus. Cell Stem Cell. DOI:10.1016/j.stem.2021.03.020 |
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