Kim Chang N, Shin David, Wang Albert, Nowakowski Tomasz J
bioRxiv. 2023 Aug 22:2023.08.21.554174. doi: 10.1101/2023.08.21.554174.
The thalamus plays a central coordinating role in the brain. Thalamic neurons are organized into spatially-distinct nuclei, but the molecular architecture of thalamic development is poorly understood, especially in humans. To begin to delineate the molecular trajectories of cell fate specification and organization in the developing human thalamus, we used single cell and multiplexed spatial transcriptomics. Here we show that molecularly-defined thalamic neurons differentiate in the second trimester of human development, and that these neurons organize into spatially and molecularly distinct nuclei. We identify major subtypes of glutamatergic neuron subtypes that are differentially enriched in anatomically distinct nuclei. In addition, we identify six subtypes of GABAergic neurons that are shared and distinct across thalamic nuclei.
ONE-SENTENCE SUMMARY: Single cell and spatial profiling of the developing thalamus in the first and second trimester yields molecular mechanisms of thalamic nuclei development.
丘脑在大脑中发挥着核心协调作用。丘脑神经元被组织成空间上不同的核团,但丘脑发育的分子结构却知之甚少,尤其是在人类中。为了开始描绘发育中的人类丘脑中细胞命运特化和组织的分子轨迹,我们使用了单细胞和多重空间转录组学技术。在这里,我们表明,分子定义的丘脑神经元在人类发育的中期分化,并且这些神经元组织成空间和分子上不同的核团。我们确定了在解剖学上不同的核团中差异富集的谷氨酸能神经元亚型的主要亚型。此外,我们确定了六种GABA能神经元亚型,它们在丘脑核团中是共享的且不同的。
对妊娠前三个月和中期发育中的丘脑进行单细胞和空间分析,得出丘脑核团发育的分子机制。