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CTBs constitute the stem\/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal\u2013fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label\u2010free liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell\u2010type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem\u2010state. Additionally, atypical protein kinase C isoforms PKC\u03b6 are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.<\/jats:p>","DOI":"10.1096\/fj.202600627rr","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:37:36Z","timestamp":1787996256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development"],"prefix":"10.1096","volume":"40","author":[{"given":"Rajnish","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Institute for Reproduction and Developmental Science University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purbasa","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Institute for Reproduction and Developmental Science University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soma","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Institute for Reproduction and Developmental Science University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-4800","authenticated-orcid":false,"given":"Soumen","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Institute for Reproduction and Developmental Science University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Obstetrics and Gynecology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0066"},{"key":"e_1_2_10_3_1","article-title":"The Human Placenta: New Perspectives on Its Formation and Function During Early Pregnancy","volume":"290","author":"Burton G. 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