{"id":5396,"date":"2026-02-25T09:46:57","date_gmt":"2026-02-25T02:46:57","guid":{"rendered":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/?p=5396"},"modified":"2026-03-30T11:30:02","modified_gmt":"2026-03-30T04:30:02","slug":"a-pyrimido-indole-derivative-promotes-the-differentiation-of-hematopoietic-stem-and-progenitor-cells-from-human-induced-pluripotent-stem-cells-by-modulating-yap-hippo-signaling-pathway","status":"publish","type":"post","link":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/a-pyrimido-indole-derivative-promotes-the-differentiation-of-hematopoietic-stem-and-progenitor-cells-from-human-induced-pluripotent-stem-cells-by-modulating-yap-hippo-signaling-pathway\/","title":{"rendered":"A pyrimido-indole derivative promotes the differentiation of hematopoietic stem and progenitor cells from human-induced pluripotent stem cells by modulating YAP\/Hippo signaling pathway"},"content":{"rendered":"<p>Palida Saleepimol, Gorawin Chaiyakitpattana, Benjamin Ongnok, <strong>Pongpon Phuwakanjana<\/strong>, Tanida Chokpanuwat, Phaewa Chaiwijit, Veeravat Changkeb, Klodthida Yanukun, Nontaphat Thongsin, Methichit Wattanapanitch, Nithi Asavapanumas, Alisa Tubsuwan, Nareerat Sutjarit, Suradej Hongeng, Kanit Bhukhai<\/p>\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<div class=\"title\">\n<p>Hematopoietic stem and progenitor cell (HSPC) therapy effectively treats hematological disorders, such as hemoglobinopathies, aplastic anemia, and leukemias. However, limited HSPC availability and loss of stemness restrict clinical application, necessitating alternative sources. Human induced pluripotent stem cells (hiPSCs) offer promise due to their pluripotency and self-renewal. However, current protocols for generating HSPCs from hiPSCs often compromise their stemness and regenerative potential. This study investigates the potential of the pyrimido-indole derivative, specifically UM729, to enhance the production and functionality of HSPCs derived from hiPSCs. UM729 treatment significantly increased HSPC (CD34+CD45+CD90+) and long-term-HSC (CD34+CD38-CD45RA-CD90+CD49f+) markers compared with DMSO control, and promoted formation of hemogenic (CD144+CD73-) and vascular endothelial (CD144+CD73+) niche progenitors. The generated HSPCs demonstrated self-renewal capacity, confirmed by long-term culture-initiating cell (LTC-IC) assay. The expanded HSPCs retained long-term-HSC marker expression for up to seven days without detectable apoptosis and remained functionally responsive, as shown by lipopolysaccharide (LPS)-induced cytokine secretion. They differentiated into myeloid and erythroid lineages, with erythroid maturation confirmed by hemoglobin gene detection, expression of erythroid transcription factors, and normal cell morphology. Mechanistically, UM729 increased YAP protein levels, a key Hippo pathway regulator, predominantly in the cytoplasm, suggesting a potential effect on pathway inhibition. Co-treatment with UM729 and the YAP\/TAZ inhibitor, dobutamine, further enhanced HSPC marker expression by up to 20-fold relative to DMSO control. These results demonstrate that UM729 supports scalable production of functional HSPCs from hiPSCs and that combination with Hippo pathway modulator may further improve yields. This approach holds promise for advancing hematopoietic stem cell-based therapies for blood diseases.<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41052706\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/41052706\/<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Palida Saleepimol, Gorawin Chaiyakitpattana, Benjamin Ongnok, Pongpon Phuwakanjana, Tanida Chokpanuwat, Phaewa Chaiwijit, Veeravat Changkeb, Klodthida Yanukun, Nontaphat Thongsin, Methichit Wattanapanitch, Nithi Asavapanumas, Alisa Tubsuwan, Nareerat Sutjarit, Suradej Hongeng, Kanit Bhukhai Abstract Hematopoietic stem and progenitor cell (HSPC) therapy effectively treats hematological disorders, such as hemoglobinopathies, aplastic anemia, and leukemias. However, limited HSPC availability and loss [&#8230;]\n","protected":false},"author":6,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-5396","post","type-post","status-publish","format-standard","hentry","category-research-innovation-en"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>A pyrimido-indole derivative promotes the differentiation of hematopoietic stem and progenitor cells from human-induced pluripotent stem cells by modulating YAP\/Hippo signaling pathway - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/a-pyrimido-indole-derivative-promotes-the-differentiation-of-hematopoietic-stem-and-progenitor-cells-from-human-induced-pluripotent-stem-cells-by-modulating-yap-hippo-signaling-pathway\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A pyrimido-indole derivative promotes the differentiation of hematopoietic stem and progenitor cells from human-induced pluripotent stem cells by modulating YAP\/Hippo signaling pathway - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"og:description\" content=\"Palida Saleepimol, Gorawin Chaiyakitpattana, Benjamin Ongnok, Pongpon Phuwakanjana, Tanida Chokpanuwat, Phaewa Chaiwijit, Veeravat Changkeb, Klodthida Yanukun, Nontaphat Thongsin, Methichit Wattanapanitch, Nithi Asavapanumas, Alisa Tubsuwan, Nareerat Sutjarit, Suradej Hongeng, Kanit Bhukhai Abstract Hematopoietic stem and progenitor cell (HSPC) therapy effectively treats hematological disorders, such as hemoglobinopathies, aplastic anemia, and leukemias. 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However, limited HSPC availability and loss [...]","og_url":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/a-pyrimido-indole-derivative-promotes-the-differentiation-of-hematopoietic-stem-and-progenitor-cells-from-human-induced-pluripotent-stem-cells-by-modulating-yap-hippo-signaling-pathway\/","og_site_name":"\u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25","article_publisher":"https:\/\/www.facebook.com\/SIBBprogram\/","article_published_time":"2026-02-25T02:46:57+00:00","article_modified_time":"2026-03-30T04:30:02+00:00","author":"Poorintra Sakuna","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Poorintra Sakuna","Est. reading time":"2 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