Activated HoxB4-induced hematopoietic stem cells from murine pluripotent stem cells via long-term programming

Autor: Arinobu Tojo, Tomoya Kakegawa, Hans Jiro Becker, Kiyoko Izawa, Momoko Sakaguchi, Joydeep Bhadury, Satoshi Yamazaki
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
medicine.medical_treatment
Induced Pluripotent Stem Cells
Primary Cell Culture
Mutant Chimeric Proteins
Mice
Transgenic
Hematopoietic stem cell transplantation
Biology
03 medical and health sciences
Mice
0302 clinical medicine
Genetics
medicine
Animals
Humans
Progenitor cell
Induced pluripotent stem cell
Molecular Biology
Cell Proliferation
Homeodomain Proteins
Stem Cell Factor
Hematopoietic Stem Cell Transplantation
hemic and immune systems
Cell Differentiation
Cell Biology
Hematology
Cellular Reprogramming
Hematopoietic Stem Cells
Embryonic stem cell
Cell biology
Hematopoiesis
Transplantation
Mice
Inbred C57BL
Haematopoiesis
Tamoxifen
030104 developmental biology
Gene Expression Regulation
Receptors
Estrogen
Thrombopoietin
Cell culture
030220 oncology & carcinogenesis
Leukocyte Common Antigens
Stem cell
Whole-Body Irradiation
Transcription Factors
Zdroj: Experimental hematology. 89
ISSN: 1873-2399
Popis: Hematopoietic stem cells (HSCs) are multipotent cells that form the entire blood system and have the potential to cure several pathogenic conditions directly or indirectly arising from defects within the HSC compartment. Pluripotent stem cells (PSCs) or induced pluripotent stem cells (iPSCs) can give rise to all embryonic cell types; however, efficient in vitro differentiation of HSCs from PSCs remains challenging. HoxB4 is a key regulator orchestrating the differentiation of PSCs into all cells types across the mesodermal lineage, including HSCs. Moreover, the ectopic expression of HoxB4 enhances the in vitro generation and expansion of HSCs. However, several aspects of HoxB4 biology including its regulatory functions are not fully understood. Here, we describe the role of HoxB4 in indirectly inhibiting the emergence of mature CD45+ HSCs from iPSCs in vitro. Forced activation of HoxB4 permitted long-term maintenance of functional hematopoietic stem and progenitor cells (HSPCs), which efficiently reconstituted hematopoiesis upon transplantation. Our method enables an easy and scalable in vitro platform for the generation of HSCs from iPSCs, which will ultimately lead to a better understanding of HSC biology and facilitate preparation of the roadma for producing an unrestricted supply of HSCs for several curative therapies.
Databáze: OpenAIRE
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