Teruyuki Kajiume1,2, Yumi Kawahara3, Louis Yuge3, Masao Kobayashi2,4. 1. Mukainada Child Clinic, Hiroshima, Japan. 2. Department of Pediatrics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. 3. Division of Bio-Environmental Adaptation Sciences, Graduate School of Health Sciences, Hiroshima University, Hiroshima, Japan. 4. Japanese Red Cross Chugoku-Shikoku Block Blood Center, Hiroshima, Japan.
Abstract
BACKGROUND: Intrinsic factors related to self-renewal regulatory factors in hematopoietic stem cells are well known; however, limited information is available on extrinsic factors, such as the cell environment. Therefore, in this study, we analyzed the regulatory mechanism of hematopoietic stem cell self-renewal, focusing on the osteoblastic niche, and examined how adherence to osteoblasts affects stem cell differentiation. METHODS: For this experimental study, we developed a co-culture system for hematopoietic stem cells and osteoblasts, such that cells adhered to osteoblasts can be separated from those that do not. Murine Sca1-positive cells were separated into groups according to whether they were attached to osteoblasts or detached from osteoblasts, and each group was then subjected to colony assays and bone marrow transplantation experiments. RESULTS: Adhered Sca1-positive cells developed more secondary colonies than non-adhered Sca1-positive cells. Furthermore, in bone marrow transplantation experiments, adhered Sca1-positive cells showed successful engraftment. We explored the role of Polycomb genes in the regulation of cell fate and found that self-renewing cells attached to osteoblasts had high Bmi-1 expression and low Mel-18 expression, while this expression was reversed in differentiating cells. CONCLUSIONS: Our results suggest that hematopoietic stem cells self-renew when they remain in osteoblastic niches after cell division. Further, when stem cells leave the niches, they undergo differentiation. 2021 Stem Cell Investigation. All rights reserved.
BACKGROUND: Intrinsic factors related to self-renewal regulatory factors in hematopoietic stem cells are well known; however, limited information is available on extrinsic factors, such as the cell environment. Therefore, in this study, we analyzed the regulatory mechanism of hematopoietic stem cell self-renewal, focusing on the osteoblastic niche, and examined how adherence to osteoblasts affects stem cell differentiation. METHODS: For this experimental study, we developed a co-culture system for hematopoietic stem cells and osteoblasts, such that cells adhered to osteoblasts can be separated from those that do not. Murine Sca1-positive cells were separated into groups according to whether they were attached to osteoblasts or detached from osteoblasts, and each group was then subjected to colony assays and bone marrow transplantation experiments. RESULTS: Adhered Sca1-positive cells developed more secondary colonies than non-adhered Sca1-positive cells. Furthermore, in bone marrow transplantation experiments, adhered Sca1-positive cells showed successful engraftment. We explored the role of Polycomb genes in the regulation of cell fate and found that self-renewing cells attached to osteoblasts had high Bmi-1 expression and low Mel-18 expression, while this expression was reversed in differentiating cells. CONCLUSIONS: Our results suggest that hematopoietic stem cells self-renew when they remain in osteoblastic niches after cell division. Further, when stem cells leave the niches, they undergo differentiation. 2021 Stem Cell Investigation. All rights reserved.
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