Abstract
The ability of stem cells to divide and differentiate is necessary for tissue repair and homeostasis. Appropriate spatial and temporal mechanisms are needed. Local intercellular signaling increases expression of specific genes that mediate and maintain differentiation. Diffusible signaling molecules provide concentration-dependent induction of specific patterns of cell types or regions. Differentiation of adjacent cells, on the other hand, requires cell–cell contact and subsequent signaling. These two types of signals work together to allow stem cells to provide what organisms require. The ability to grow organoids has increased our understanding of the cellular and molecular features of small “niches” that modulate stem cell function in various organs, including the small intestine.
Highlights
The intestinal epithelium undergoes rapid and continuous self-renewal, cell commitment, and cell differentiation along the crypt-villus axis throughout postnatal life
Paneth cells are intestinal epithelial cells that control stem cells via production of bactericidal products [2] and expression of critical niche signals such as epidermal growth factor, transforming growth factor-α, Wnt3, and delta-like ligand 4 (Dll4), which is the ligand for Notch [3]
A core component of MOB1A/B in the Hippo signaling pathway coordinates with Bone Morphogenetic Protein (BMP)/transforming growth factor (TGF)-β signaling, the activation of which results in inhibition of Wnt activity in the crypt region and loss of intestinal epithelial homeostasis [59]
Summary
The intestinal epithelium undergoes rapid and continuous self-renewal, cell commitment, and cell differentiation along the crypt-villus axis throughout postnatal life. Marked leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)+ cells persist for the lifetime in mice, whereas their progeny includes all differentiated cell lineages of the epithelium (Figure 1B) [7]. B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) marks quiescent ISCs, which are located at position +4 from the base of the crypt (Figure 1B). Gre-cperpottoerin c[o9]u.pled receptor 5 [9] Both development of the small intestine and homeostasis of the adult gut require canonical Wnt Bsiogtnhaldinevgeilnovpomlveinntgoβf-cthaetensminaallndintthesetiTn-eceallnfdachtoorm/lyeomsptahsoisido-fenthheanacdeur-lbt ignudtinrgeqfaucirtoercfaanmoinlyicoalf Wtranntsscirginpatiloinngfiancvtoorlsvi[n1g0–β1-4c]a.tePnrionliafenrdattihoenTi-ncethllefaccrtyopr/tlsyims pcohmoipdr-oenmhiasnedceirn-bminidceinlgacfkacintogrcfaanmoinlyicoafl tWranntscpraipthtiwonayfamctoolrescu[1le0s–1[145].].PrTohliefecreantitoranl irnoltehoefcWrynpttssiigsncaolminpgriosmhiisgehdliignhtmedicebylaWcknintg-dceapneonndiecnalt Wexnptrepsastiohnwoayf nmumoleecrouulessI[S1C5]m. This review will discuss how ISC division, differentiation, and homeostasis are controlled, how stem cell signaling affects the cell’s position in the crypt-villus axis, and the importance of these observations in development
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