Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

Abstract

The neuroendocrine hypothalamus is the central regulator of vital physiological homeostasis and behavior. However, the cellular and molecular properties of hypothalamic neural progenitors remain unexplored. Here, hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells are found to be neural progenitors in the developing mammalian hypothalamus. The hmRG cells originate from hRG cells and produce neurons. During the early development of hypothalamus, neurogenesis occurs in radial columns and is initiated from hRG cells. The radial glial fibers are oriented toward the locations of hypothalamic subregions which act as a scaffold for neuronal migration. Furthermore, we use single-cell RNA sequencing to reveal progenitor subtypes in human developing hypothalamus and characterize specific progenitor genes, such as TTYH1 , HMGA2 , and FAM107A . We also demonstrate that HMGA2 is involved in E2F1 pathway, regulating the proliferation of progenitor cells by targeting on the downstream MYBL2. Different neuronal subtypes start to differentiate and express specific genes of hypothalamic nucleus at gestational week 10. Finally, we reveal the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. Our identification of cellular and molecular properties of neural progenitors provides a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus.

Decoding neuronal composition and ontogeny of individual hypothalamic nuclei

“…Little is known about the role of individual hypothalamic progenitor lineages in the development of hypothalamic nuclei (Zhou et al, 2020). Taking advantage of the sparse MADM labeling system for clonal lineage analysis and TF combinations for neuronal subpopulation identification, our study revealed that the pArc progenitors are multipotent and can generate highly diverse lineage types consisting of various combinations of Arc1-4 subpopulations of different numbers.…”

Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors

“…The availability of scRNA-Seq from early stages of mouse and human hypothalamic neurogenesis makes it possible to directly compare these chick neuronal precursor clusters to clusters previously annotated in E11-E13 mouse (Kim et al, 2020) and gestational week 10 human hypothalamus (Zhou et al, 2020). Tuberal clusters (C0, C1, and C3) closely matched mouse arcuate and ventromedial hypothalamic clusters, as well as the human tuberal hypothalamic cluster (Fig.…”

“…To identify the correlation between chicken, mouse, and human, post-mitotic hypothalamic cells from HH18 and HH20 (this work), E11-E13 mouse scRNA-Seq (Kim et al, 2020), and gestational week 10 human scRNA-Seq (Zhou et al, 2020) were used. Annotation of the human scRNA-Seq dataset was based on a mouse scRNA-Seq database and as shown in the original publication.…”

The target E2F family gene PTTG1 for prediction of distant relapse-free survival in breast cancer patients receiving taxane and anthracycline-based NACT

“…Anthracyclines and taxanes serve as the backbone of NACT regimens and are widely used clinically in breast cancer patients [5]. It has been proved that the E2F family of transcription factor are synergistically involved in regulating cell-cycle progression [6], controlling cell proliferation, apotosis [7] and DNA repair with consequent effects on cell growth or tumor cell invasion [8][9][10][11][12].…”