Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways

Abstract

Signaling networks guide stem cells during their lineage specification and terminal differentiation. Primary cilium, an antenna-like protrusion, directly or indirectly plays a significant role in this guidance. All stem cells characterized so far have primary cilia. They serve as entry- or check-points for various signaling events by controlling the signal transduction and stability. Thus, defects in the primary cilia formation or dynamics cause developmental and health problems, including but not limited to obesity, cardiovascular and renal anomalies, hearing and vision loss, and even cancers. In this review, we focus on the recent findings of how primary cilium controls various signaling pathways during stem cell differentiation and identify potential gaps in the field for future research.

Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna

“…Abnormal cilia formation or function resulting from genetic mutations are called Ciliopathies. Ciliopathies are heterogeneous diseases that can affect almost all organs as primary cilia can be formed in every cell of the human body from stem cells ( Yanardag and Pugacheva, 2021 ), to neurons ( Dahl, 1963 ; Handel et al, 1999 ; Bishop et al, 2007 ), epithelial cells in different organs ( Jain et al, 2010 ; Rocha et al, 2014 ), and blood and bone marrow cells ( Singh et al, 2016 ). Thus, alterations in primary cilia can lead to a range of different phenotypes.…”

Ciliary membrane, localised lipid modification and cilia function

“…Consistent with this notion, recent studies in adipose progenitor cells have shown that caveolin −1 (CAV1), a marker of lipid rafts and GM3, localises at the base of the primary cilia immediately after adipogenic stimulation, activating the insulin‐Akt signalling cascade. Downregulation of this signalling cascade, which reduced CAV1 and GM3 accumulation at the ciliary base, was associated with cilia loss and Aurora‐A kinase activation (Yamakawa et al, 2021). Thus, the dynamics of lipid raft assembly and GM3 synthesis could also drive the growth and functioning of the cilia.…”

“…The cilia‐dependent signalling repertoire includes some of the primary regulators of cell proliferation, such as the hedgehog (Hh), wingless (Wnt), G‐protein coupled receptors (GPCRs) and a variety of growth factor receptors active during development and in differentiated tissues (Wingfield et al, 2018). The ciliary localisation of GPCRs like the serotonin (HTR6) and somatostatin (SSTR3) receptors, the transient receptor potential (TRP) superfamily members like the polycystin (PC1/2) family, and cyclic nucleotide‐gated (CNG) channels also contribute to the physiological conditioning of the cell under different environmental situations (Barbeito & Garcia‐Gonzalo, 2021; Yanardag & Pugacheva, 2021). The growth, stability and resorption of cilia are strongly correlated with cell proliferation, homeostasis and function.…”

Primary Cilia Are Critical Regulators of White Adipose Tissue Expansion

“…All characterized stem and progenitor cells in the human body are ciliated ( Yanardag and Pugacheva, 2021 ). This includes the embryonic stem cell, mesenchymal stem cells (MSCs), and all committed progenitor cells in the mesenchymal lineages giving rise to adipose tissue, muscle, bone, and cartilage.…”

“…The primary cilium is a sensory organelle that is highly conserved throughout eukaryotic evolution and found on most mammalian cells ( Goetz and Anderson, 2010 ). All cells in the human body are either ciliated or derived from a ciliated stem cell ( Yanardag and Pugacheva, 2021 ). Cilia are critical to human development and physiology by organizing signal transduction pathways such as hedgehog signaling in vertebrate cells ( Kopinke et al, 2021 ).…”