Data Availability StatementData sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Results In CRC cell lines, the proportion of ALDH+ cells inversely correlates with proportion of SSTR1+ cells and with rate of proliferation and sphere-formation. While primary normal tissue shows SST and SSTR1 expression, CRC shows only SSTR1 expression. Moreover, ALDH+ cells did not show SST or SSTR1 expression. Exogenous SST suppressed proliferation but not ALDH+ population size or viability. Inhibition of SSTR1 signaling, via cycloSST treatment, decreased cell proliferation, ALDH+ cell population size and sphere-formation. When co-cultured with SSTR1+ cells, sphere-formation and cell proliferation of ALDH+ cells was inhibited. Conclusion That each CRC cell line has a unique ALDH+/SSTR1+ ratio which correlates with its growth dynamics, suggests feedback mechanisms exist between SCs and NECs that contribute to regulation of SCs. The growth suppression by both SST and cycloSST treatments suggests that SST signaling modulates this feedback mechanism. The ability of SSTR1+ cells to decrease sphere formation and proliferation of ALDH+ cells in transwell cultures indicates that the ALDH subpopulation is regulated by SSTR1 via a paracrine mechanism. Since ALDH+ cells lack SST and SSTR1 expression, we conjecture that SST signaling Elf2 controls the rate of NEC maturation as SCs mature along the NEC lineage, which contributes to quiescence of SCs and inhibition of proliferation. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2969-7) contains supplementary material, which is available to authorized users. Background In colorectal cancer (CRC) development, the overpopulation of neoplastic stem cells (SCs) appears to drive tumor initiation and progression, but it is not really known which specific mechanisms that regulate normal colonic SCs, when dysregulated, LY364947 result in SC overpopulation in CRC [1C4]. We surmised that the interactions and communication between different cell types within the colonic crypt SC niche may be crucial to regulation of normal SCs. Specific types of neuroendocrine cells (NECs), such as somatostatin receptor 1 cells (SSTR1), have been shown to reside in close proximity to colonic SCs in the niche at the bottom of the normal human colonic crypt (see Additional file 1: Figure S1). NECs are known to function in inhibition and/or enhancement of cell proliferation either by paracrine or autocrine signaling [5C8]. Nonetheless, the mechanisms through which SCs and specific NECs interact with each LY364947 other in the normal colon have not been extensively studied. We hypothesize that SSTR1 cells maintain colonic SCs in a quiescent state, and aberrant SST signaling contributes to SC overpopulation in CRC. Indeed, a substantial body of evidence reveals that various types of NECs are located along the normal intestinal tract and each NEC subtype has a different effect on neighboring cells [6, 7, 9, 10]. Specific NEC functions include secretion of peptides to act in a paracrine or autocrine fashion to exert local effects on cell proliferation and differentiation, or exert distant effects by endocrine secretion [7]. These NECs are often selectively located within the SC niche where the colonic SCs reside in a quiescent state. Thus, the niche likely LY364947 provides the cues underlying slow-cycling dynamics of the SC population and asymmetric SC division that maintains the hierarchical nature of differentiated cell lineages in the colonic crypt [2]. Of note, colonic NECs do not appear to follow the classical hierarchical model of SC differentiation and are thought to arise by direct differentiation of a colonic SC, again supporting the close interactions between the two cell types [8]. Consequently, it seems feasible that the communication between NECs and colonic SCs is crucial to normal crypt homeostasis and maintenance of the quiescent nature of colonic SCs, and that dysregulation of the interactions and communication between the cell types could lead to colonic SC overpopulation during CRC.