Uncovering the emergence of HSCs in the human fetal bone marrow by single-cell RNA-seq analysis

Zheng, Zhaofeng; He, Han; Tang, Xinyu Thomas; Zhang, Han; Gou, Fanglin; Yang, Hua; Cao, Jiaxuan; Shi, Shujuan; Yang, Zining; Sun, Guohuan; Xie, Xiaowei; Zeng, Yang; Wen, Aiyou; Lan, Yu; Zhou, Jiaxi; Liu, Bing; Zhou, Bo; Cheng, Tao; Cheng, Hui

doi:10.1016/j.stem.2022.10.005

Cited by 24 publications

(22 citation statements)

References 74 publications

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“…[ 62 ] Recent work suggests functional HSCs do not emerge in human BM until 12 post‐conception weeks. [ 63 ] Similar to mice, arterial endothelial cells are important sources of many niche factors in human fetal BM. [ 63 ] The average distance of HSCs to arterial endothelial cells increases from E16.5 to E18.5 in mice, suggesting that HSCs gradually migrate away from arterial endothelial cells to disperse into other areas of BM after their initial engraftment.…”

Section: The Dynamic Switch Of Hscs Niches From Fetal Adult To Aging ...mentioning

confidence: 99%

“…[63] Similar to mice, arterial endothelial cells are important sources of many niche factors in human fetal BM. [63] The average distance of HSCs to arterial endothelial cells increases from E16.5 to E18.5 in mice, suggesting that HSCs gradually migrate away from arterial endothelial cells to disperse into other areas of BM after their initial engraftment. [62] This distribution pattern of HSCs and HSPCs in fetal BM is in sharp contrast with the location of HSPCs after transplantation, in which HSPCs preferentially locate in the endosteum or diaphyseal area of BM without apparent association with the artery.…”

Section: Engraftment Of Hscs Into Fetal and Adult Bmmentioning

confidence: 99%

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Dynamic crosstalk between hematopoietic stem cells and their niche from emergence to aging

Deng

Chen

et al. 2023

BioEssays

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The behavior of somatic stem cells is regulated by their niche. Interaction between hematopoietic stem cells (HSCs) and their niches are a representative model to understand stem cell‐niche interplay. Here, we provide an overview of crosstalk between HSCs and their niches in bone marrow and extramedullary organs following the life journey of HSCs from emergence, development, maturation until aging. We highlight the unique differences of HSC niches in different life stages within various organs focusing on recent literature to propose new speculations and hypotheses.

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Section: The Dynamic Switch Of Hscs Niches From Fetal Adult To Aging ...mentioning

confidence: 99%

Section: Engraftment Of Hscs Into Fetal and Adult Bmmentioning

confidence: 99%

Dynamic crosstalk between hematopoietic stem cells and their niche from emergence to aging

Deng

Chen

et al. 2023

BioEssays

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“…7 The advancement of single-cell systems biology research technology has provided tools to address these issues, capturing the instantaneous states of stem cells in multiple differentiation directions at specific time points. [8][9][10] Our prior study employed single-cell RNA sequencing (scRNA-seq) to observe the multidirectional continuous differentiation of stromal cells within the bone marrow microenvironment in conditions such as osteonecrosis, osteoarthritis (OA), and osteoporotic fractures. 11 These findings highlighted the potential of scRNA-seq to investigate BMSC differentiation abnormalities in OP.…”

Section: Introductionmentioning

confidence: 99%

Carboxypeptidase M modulates BMSCs osteogenesis–adipogenesis via the MAPK/ERK pathway: An integrated single‐cell and bulk transcriptomic study

Liao,

Zheng,

et al. 2024

The FASEB Journal

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The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow‐derived mesenchymal stem cells (BMSCs). We analyzed published single‐cell RNA sequencing (scRNA‐seq) data to dissect the transcriptomic profiles of bone marrow‐derived cells in OP, reviewing 56 377 cells across eight scRNA‐seq datasets from femoral heads (osteoporosis or osteopenia n = 5, osteoarthritis n = 3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis‐adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus‐mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM‐overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA‐seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM‐mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provides new clues for the mechanistic study of OP.

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“…Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche, where they depend on various cell types, such as endothelial cells (ECs) and perivascular mesenchymal cells, for survival and differentiation signals. [1][2][3] The BM niche plays a crucial role in regulating leukemia cell behavior, [4][5][6] implicating competition between HSCs and leukemia cells for the same niche. 7 Furthermore, leukemia cells can restructure the surrounding environment to establish a unique leukemia-permissive niche, which sustains leukemia cell survival at the expense of normal hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia

et al. 2023

Blood Science

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Leukemia stem cells in acute myeloid leukemia (AML) can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy. In the context of AML, endothelial cells (ECs) are crucial components of these niches that appear to promote malignant expansion despite treatment. To better understand these interactions, we developed a real-time cell cycle-tracking mouse model of AML (Fucci-MA9) with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse. We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells, leading to relapse and proliferation. Importantly, post-chemotherapy resting leukemia cells tended to localize closer to blood vessels. Mechanistically, after chemotherapy, resting leukemia cells interacted with ECs, promoting their adhesion and anti-apoptotic capacity. Further, expression analysis of ECs and leukemia cells during AML, after chemotherapy, and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs. These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.

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Uncovering the emergence of HSCs in the human fetal bone marrow by single-cell RNA-seq analysis

Cited by 24 publications

References 74 publications

Dynamic crosstalk between hematopoietic stem cells and their niche from emergence to aging

Dynamic crosstalk between hematopoietic stem cells and their niche from emergence to aging

Carboxypeptidase M modulates BMSCs osteogenesis–adipogenesis via the MAPK/ERK pathway: An integrated single‐cell and bulk transcriptomic study

Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia

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