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Presently, the most common treatment for ED is phosphodiesterase 5 inhibitors; however, this is less effective in patients with severe vascular disease such as diabetic ED. Therefore, there is a need for development of new treatment, which requires a better understanding of the cavernous microenvironment and cell-cell communications under diabetic condition. Pericytes are vital in penile erection; however, their dysfunction due to diabetes remains unclear. In this study, we performed single-cell RNA sequencing to understand the cellular landscape of cavernous tissues and cell type-specific transcriptional changes in diabetic ED. We found a decreased expression of genes associated with collagen or extracellular matrix organization and angiogenesis in diabetic fibroblasts, chondrocytes, myofibroblasts, valve-related lymphatic endothelial cells, and pericytes. Moreover, the newly identified pericyte-specific marker, Limb Bud-Heart (Lbh)\n                    <jats:italic>,<\/jats:italic>\n                    in mouse and human cavernous tissues, clearly distinguishing pericytes from smooth muscle cells. Cell-cell interaction analysis revealed that pericytes are involved in angiogenesis, adhesion, and migration by communicating with other cell types in the corpus cavernosum; however, these interactions were highly reduced under diabetic conditions. Lbh expression is low in diabetic pericytes, and overexpression of LBH prevents erectile function by regulating neurovascular regeneration. Furthermore, the LBH-interacting proteins (Crystallin Alpha B and Vimentin) were identified in mouse cavernous pericytes through LC-MS\/MS analysis, indicating that their interactions were critical for maintaining pericyte function. Thus, our study reveals novel targets and insights into the pathogenesis of ED in patients with diabetes.\n                  <\/jats:p>","DOI":"10.7554\/elife.88942","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T10:39:57Z","timestamp":1693564797000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.88942","source":"Crossref","is-referenced-by-count":17,"title":["Single-cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-3783","authenticated-orcid":true,"given":"Seo-Gyeong","family":"Bae","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024kbgz78","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Sciences, Gwangju Institute of Science and Technology (GIST)","place":["Gwangju, Republic of 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