{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:53:40Z","timestamp":1760144020836,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jans Graduate Scholarship","award":["FRN 159925"],"award-info":[{"award-number":["FRN 159925"]}]},{"name":"Michael G. DeGroote Doctoral Scholarship","award":["FRN 159925"],"award-info":[{"award-number":["FRN 159925"]}]},{"name":"Ontario Graduate Scholarship","award":["FRN 159925"],"award-info":[{"award-number":["FRN 159925"]}]},{"name":"Canadian Institutes of Health Research","award":["FRN 159925"],"award-info":[{"award-number":["FRN 159925"]}]},{"name":"Ontario Graduate Fellowship","award":["FRN 159925"],"award-info":[{"award-number":["FRN 159925"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The generation of human hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) represents a major goal in regenerative medicine and is believed would follow principles of early development. HSCs arise from a type of endothelial cell called a \u201chemogenic endothelium\u201d (HE), and human HSCs are experimentally detected by transplantation into SCID or other immune-deficient mouse recipients, termed SCID-Repopulating Cells (SRC). Recently, SRCs were detected by forced expression of seven transcription factors (TF) (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, and SPI1) in hPSC-derived HE, suggesting these factors are deficient in hPSC differentiation to HEs required to generate HSCs. Here we derived PECAM-1-, Flk-1-, and VE-cadherin-positive endothelial cells that also lack CD45 expression (PFVCD45\u2212) which are solely responsible for hematopoietic output from iPSC lines reprogrammed from AML patients. Using HEs derived from AML patient iPSCs devoid of somatic leukemic aberrations, we sought to generate putative SRCs by the forced expression of 7TFs to model autologous HSC transplantation. The expression of 7TFs in hPSC-derived HE cells from an enhanced hematopoietic progenitor capacity was present in vitro, but failed to acquire SRC activity in vivo. Our findings emphasize the benefits of forced TF expression, along with the continued challenges in developing HSCs for autologous-based therapies from hPSC sources.<\/jats:p>","DOI":"10.3390\/cells11121915","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"1915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Challenges in Cell Fate Acquisition to Scid-Repopulating Activity from Hemogenic Endothelium of hiPSCs Derived from AML Patients Using Forced Transcription Factor Expression"],"prefix":"10.3390","volume":"11","author":[{"given":"Deanna P.","family":"Porras","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer C.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borko","family":"Tanasijevic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Golubeva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison L.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mickie","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada"},{"name":"Michael G. DeGroote School of Medicine, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ni.1889","article-title":"Revised Map of the Human Progenitor Hierarchy Shows the Origin of Macrophages and Dendritic Cells in Early Lymphoid Development","volume":"11","author":"Doulatov","year":"2010","journal-title":"Nat. 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