Hes1, short for Hairy and enhancer of split homolog-1, is a member of the basic helix-loop-helix (bHLH) protein family. It functions as a transcription factor and is crucial in regulating cell cycle, proliferation, differentiation, survival, and apoptosis in various cell types such as neuronal, endocrine, T-lymphocyte progenitors, and in cancer cells [1]. It is regulated by signaling pathways like NOTCH, Hedgehog, and Wnt, which are often aberrant in cancer [1]. Gene knockout models, especially in mice, have been instrumental in understanding its functions.

In a hematopoietic lineage-specific Hes1 knockout mouse model, Hes1-deficient hematopoietic stem cells (HSCs) underwent exhaustion under replicative stress, indicating its role in stress hematopoiesis and HSC maintenance [2]. In human embryonic stem cells with endogenously introduced HES1 -/- mutations, there was impaired development of intestinal mesenchymal cells due to down-regulation of WNT5A signaling, suggesting its importance in human intestinal development [3]. In neural stem cells (NSCs), overexpression of active Notch1 induced a burst of Hes1 oscillations in quiescent NSCs, with the oscillation frequency correlating with NSC activation, highlighting its role in NSC state transition [4].

In conclusion, Hes1 is essential in multiple biological processes including hematopoiesis, intestinal development, and neural stem cell regulation. Studies using Hes1 knockout or conditional knockout mouse models have provided insights into its roles in these processes, as well as its implications in diseases such as cancer. These models have been crucial in revealing the molecular mechanisms underlying Hes1-mediated functions, contributing to our understanding of normal development and disease pathogenesis.

References:

1. Rani, Aradhana, Greenlaw, Roseanna, Smith, Richard A, Galustian, Christine. 2016. HES1 in immunity and cancer. In Cytokine & growth factor reviews, 30, 113-7. doi:10.1016/j.cytogfr.2016.03.010. https://pubmed.ncbi.nlm.nih.gov/27066918/

2. Ma, Zhilin, Xu, Jian, Wu, Limei, Li, Xue, Du, Wei. 2020. Hes1 deficiency causes hematopoietic stem cell exhaustion. In Stem cells (Dayton, Ohio), 38, 756-768. doi:10.1002/stem.3169. https://pubmed.ncbi.nlm.nih.gov/32129527/

3. Hu, Jianmin, Li, Jin, Dai, Can, Dai, Congling, Zeng, Sicong. 2023. HES1 deficiency impairs development of human intestinal mesenchyme by suppressing WNT5A expression. In Biochemical and biophysical research communications, 655, 50-58. doi:10.1016/j.bbrc.2023.03.014. https://pubmed.ncbi.nlm.nih.gov/36933307/

4. Kaise, Takashi, Kageyama, Ryoichiro. 2021. Hes1 oscillation frequency correlates with activation of neural stem cells. In Gene expression patterns : GEP, 40, 119170. doi:10.1016/j.gep.2021.119170. https://pubmed.ncbi.nlm.nih.gov/33675998/