Developmental Biology Laboratory Group Leader Contact Details To find out more about Naoki Nakayama, MSc, PhD, click here. Lab MembersMakoto Tanaka - Post-Doctoral Research Scientist Research FocusDevelopmental biology of adult stem cells. OverviewThe Developmental Biology laboratory’s long-standing interest is to understand how multipotent adult stem cells (ASCs) such as mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are developed from pluripotent inner cell mass/embryonic stem cells (ESCs). Developmental biology of most ASCs is still in its infant stage, except that embryonic development of HSCs is well documented. We are particularly interested in cellular pathways and associated signaling events leading to the development of HSCs and MSCs from pluripotent cells. MSCs have been defined in vitro based on their capability in generating bone, cartilage, fat and muscle cells, and HSCs are well known for their potential to give rise to lymphohematopoietic cells and to repopulate adult marrow. These cells are originated mostly from mesoderm, except that specialized bone and cartilage are derived from neural crest. Taking advantage of the ESC differentiation model in combination with bioassay, fluorescence-activated cell sorting and transcriptional profiling technologies, our strategy has been 1) to define environmental signals that allow ESCs to differentiate effectively into a particular type of mesoderm and neural crest (i.e. ASC-precursor candidates), 2) to establish methodologies to isolate them and 3) to determine the stem cell activity, as well as their lineage and positional identities. Previously, we established a scalable serum-free culture method for mouse ESCs, in which lymphohematopoietic progenitor development becomes dependent on exogenously added factors. Using cell surface markers and developmental factors we have also established methodologies to prepare cells enriched in osteochondrogenic, cardiomyogenic and/or hemoangiogenic mesoderm. Developmental potential of embryonic cells is restricted, by where they are developed and migrated in the embryo: e.g. extraembryonic mesoderm for yolk sac hematopoiesis and angiogenesis, anterior lateral mesoderm for cardiomyogenesis, and anterior neural crest for cranial bone and cartilage, etc. For the last few years, our laboratory has aimed at understanding how the developmental factors affect position-restricted subtypes of mesoderm and neural crest cells to be generated from ESCs. Biological properties of the ESC-derived ASCs will be tested in embryo models and adult disease models in future to help establish ESCs as a versatile source for cellular therapeutics. Selected PublicationsTanaka M, Wang Y, Wood C, Brouard N, Daly R, Davidson K, et al. Mesoderm generation and positional specification by Wnt and BMP during embryonic stem cell differentiation. 2006 submitted. |
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