Mapping Distinct Bone Marrow Niche Populations and Their Differentiation Paths

Wolock, Samuel L.; Krishnan, Indira; Tenen, Danielle; Matkins, Victoria; Camacho, Virginia; Patel, Sweta B.; Agarwal, Puneet; Bhatia, Ravi; Tenen, Daniel G.; Klein, Allon M.; Welner, Robert S.

doi:10.1016/j.celrep.2019.06.031

Cited by 184 publications

(161 citation statements)

References 62 publications

(82 reference statements)

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“…In this context, some recent studies have performed extensive single-cell sequencing on both the normal and preleukemic bone marrow stromal cell populations to determine both the niche of normal HSCs and how it is altered with the initiation of cancer (Baryawno et al, 2019; Wolock et al, 2019). These show that during initiation, leukemias disrupt and alter the niche (Baryawno et al, 2019), consistent with earlier studies showing that CML stem cells can disrupt osteoblast proliferation, leading to increased fibrosis and a supportive growth environment for LSCs at the expense of HSCs (Schepers et al, 2013).…”

Section: Future Directionsmentioning

confidence: 99%

Stem cells in cancer initiation and progression

Bajaj

Diaz

Reya

2019

Journal of Cell Biology

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While standard therapies can lead to an initial remission of aggressive cancers, they are often only a transient solution. The resistance and relapse that follows is driven by tumor heterogeneity and therapy-resistant populations that can reinitiate growth and promote disease progression. There is thus a significant need to understand the cell types and signaling pathways that not only contribute to cancer initiation, but also those that confer resistance and drive recurrence. Here, we discuss work showing that stem cells and progenitors may preferentially serve as a cell of origin for cancers, and that cancer stem cells can be key in driving the continued growth and functional heterogeneity of established cancers. We also describe emerging evidence for the role of developmental signals in cancer initiation, propagation, and therapy resistance and discuss how targeting these pathways may be of therapeutic value.

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Section: Future Directionsmentioning

confidence: 99%

Stem cells in cancer initiation and progression

Bajaj

Diaz

Reya

2019

Journal of Cell Biology

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“…N ew technologies enable investigators to characterize the transcriptomes of thousands of individual cells in a single experiment. (1)(2)(3) These technologies are collectively referred to as single cell RNA sequencing (scRNA-Seq) and have been used to determine the diversity of cell types in a complex tissue, (1,(4)(5)(6)(7) identify novel cell types, (8,9) and identify cells at different stages of differentiation. (10)(11)(12)(13) We determined the utility of using scRNA-Seq to detect changes in the abundance, differentiation, and transcriptional activity of cells recovered from neonatal mouse calvarium and adult mouse long bone endosteum.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell RNA Sequencing of Calvarial and Long-Bone Endocortical Cells

Ayturk

Scollan

Ayturk

et al. 2020

Journal of Bone and Mineral Research

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Single-cell RNA sequencing (scRNA-Seq) is emerging as a powerful technology to examine transcriptomes of individual cells. We determined whether scRNA-Seq could be used to detect the effect of environmental and pharmacologic perturbations on osteoblasts. We began with a commonly used in vitro system in which freshly isolated neonatal mouse calvarial cells are expanded and induced to produce a mineralized matrix. We used scRNA-Seq to compare the relative cell type abundances and the transcriptomes of freshly isolated cells to those that had been cultured for 12 days in vitro. We observed that the percentage of macrophage-like cells increased from 6% in freshly isolated calvarial cells to 34% in cultured cells. We also found that Bglap transcripts were abundant in freshly isolated osteoblasts but nearly undetectable in the cultured calvarial cells. Thus, scRNA-Seq revealed significant differences between heterogeneity of cells in vivo and in vitro. We next performed scRNA-Seq on freshly recovered long bone endocortical cells from mice that received either vehicle or sclerostin-neutralizing antibody for 1 week. We were unable to detect significant changes in bone anabolism-associated transcripts in immature and mature osteoblasts recovered from mice treated with sclerostin-neutralizing antibody; this might be a consequence of being underpowered to detect modest changes in gene expression, because only 7% of the sequenced endocortical cells were osteoblasts and a limited portion of their transcriptomes were sampled. We conclude that scRNA-Seq can detect changes in cell abundance, identity, and gene expression in skeletally derived cells. In order to detect modest changes in osteoblast gene expression at the single-cell level in the appendicular skeleton, larger numbers of osteoblasts from endocortical bone are required.

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“…New technologies enable investigators to characterize the transcriptomes of thousands of individual cells in a single experiment[1-3]. These technologies are collectively referred to as single cell RNA sequencing (scRNA-seq) and have been used to determine the diversity of cell types in a complex tissue[1, 4-7], identify novel cell types [8, 9], and identify cells at different stages of differentiation[10-13]. We determined the utility of using scRNA-seq to detect changes in the abundance, differentiation, and transcriptional activity of cells recovered from neonatal mouse calvarium and adult mouse long bone endosteum.…”

Section: Introductionmentioning

confidence: 99%

Single cell RNA sequencing of calvarial and long bone endocortical cells

Ayturk

Scollan

Vesprey

et al. 2019

Preprint

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Single cell RNA-seq (scRNA-seq) is emerging as a powerful technology to examine transcriptomes of individual cells. We determined whether scRNA-seq could be used to detect the effect of environmental and pharmacologic perturbations on osteoblasts. We began with a commonly used in vitro system in which freshly isolated neonatal mouse calvarial cells are expanded and induced to produce a mineralized matrix. We used scRNA-seq to compare the relative cell type abundances and the transcriptomes of freshly isolated cells to those that had been cultured for 12 days in vitro. We observed that the percentage of macrophage-like cells increased from 6% in freshly isolated calvarial cells to 34% in cultured cells. We also found that Bglap transcripts were abundant in freshly isolated osteoblasts but nearly undetectable in the cultured calvarial cells. Thus, scRNA-seq revealed significant differences between heterogeneity of cells in vivo and in vitro. We next performed scRNA-seq on freshly recovered long bone endocortical cells from mice that received either vehicle or Sclerostin-neutralizing antibody for 1 week. Bone anabolism-associated transcripts were also not significantly increased in immature and mature osteoblasts recovered from Sclerostin-neutralizing antibody treated mice; this is likely a consequence of being underpowered to detect modest changes in gene expression, since only 7% of the sequenced endocortical cells were osteoblasts, and a limited portion of their transcriptomes were sampled. We conclude that scRNA-seq can detect changes in cell abundance, identity, and gene expression in skeletally derived cells. In order to detect modest changes in osteoblast gene expression at the single cell level in the appendicular skeleton, larger numbers of osteoblasts from endocortical bone are required.

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Mapping Distinct Bone Marrow Niche Populations and Their Differentiation Paths

Cited by 184 publications

References 62 publications

Stem cells in cancer initiation and progression

Stem cells in cancer initiation and progression

Single-Cell RNA Sequencing of Calvarial and Long-Bone Endocortical Cells

Single cell RNA sequencing of calvarial and long bone endocortical cells

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