Single-cell RNA sequencing deconvolutes the in vivo heterogeneity of human bone marrow-derived mesenchymal stem cells

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(15), P. 4192 - 4206

Published: Jan. 1, 2021

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal that have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and fat bone marrow.In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, adipocyte crucial metabolism.While high cell-to-cell heterogeneity gene expression, cell subtypes contribute this vivo humans not been characterized.To investigate transcriptional diversity BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271 + BM-derived mononuclear (BM-MNCs) from two human subjects.We successfully identified LEPR hi CD45 low within BM-MNC population, further codified distinct subpopulations corresponding osteogenic, chondrogenic, adipogenic differentiation trajectories, well terminal-stage quiescent cells.Biological functional annotations transcriptomes suggest osteoblast precursors induce angiogenesis coupled with osteogenesis, chondrocyte potential myocytes.We also discovered transcripts several clusters (CD) markers were either highly expressed (e.g., CD167b, CD91, CD130 CD118) or absent CD74, CD217, CD148 CD68) representing novel BM-MSC purification.This study is first systematic dissection at resolution, revealing an insight extent their cellular roles maintaining homeostasis.

Language: Английский

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Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1462 - 1462

Published: June 10, 2021

Articular cartilage is a connective tissue lining the surfaces of synovial joints. When severely wears down, it leads to osteoarthritis (OA), debilitating disease that affects millions people globally. The articular composed dense extracellular matrix (ECM) with sparse distribution chondrocytes varying morphology and potentially different functions. Elucidating molecular functional profiles various chondrocyte subtypes understanding interplay between these other cell types in joint will greatly expand our biology OA pathology. Although recent advances high-throughput OMICS technologies have enabled molecular-level characterization tissues organs at an unprecedented resolution, thorough profiling has not yet been undertaken, which may be part due technical difficulties isolating from ECM. In this study, we profiled healthy injured mouse knee joints single-cell resolution identified nine distinct injury-induced early changes chondrocytes. We also compared subpopulations human evaluated extent similarity mice humans. This work expands view heterogeneity rapid populations response trauma highlights potential mechanisms trigger degeneration.

Language: Английский

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Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 1, 2021

Some osteoblasts embed within bone matrix, change shape, and become dendrite-bearing osteocytes. The circuitry that drives dendrite formation during "osteocytogenesis" is poorly understood. Here we show deletion of Sp7 in osteocytes causes defects osteocyte dendrites. Profiling target genes binding sites reveals unexpected repurposing this transcription factor to drive formation. Osteocrin a gene promotes rescues Sp7-deficient mice. Single-cell RNA-sequencing demonstrates maturation the absence Sp7. Sp7-dependent networks are associated with human skeletal diseases. Moreover, humans SP7

Language: Английский

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The Hematopoietic Bone Marrow Niche Ecosystem

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: July 22, 2021

The bone marrow (BM) microenvironment, also called the BM niche, is essential for maintenance of fully functional blood cell formation (hematopoiesis) throughout life. Under physiologic conditions niche protects hematopoietic stem cells (HSCs) from sustained or overstimulation. Acute chronic stress deregulates hematopoiesis and some these alterations occur indirectly via niche. Effects on include skewing its cellular composition, specific localization molecular signals that differentially regulate function HSCs their progeny. Importantly, while acute insults display only transient effects, repeated lead to resulting in HSC deregulation. We here describe how changes composition (ecosystem) structure (remodeling) modulate activation situ. Current knowledge has revealed upon stimulation, remodeling more extensive otherwise quiescent may be lost due diminished processes, such as autophagy, ER response, DNA repair. Features aging ecology consequence intermittent responses, ultimately degeneration supportive microenvironment. Both impair functionality increase overall susceptibility development diseases, including malignant transformation. To understand degeneration, an important prerequisite define distinguishing features unperturbed homeostasis different settings. A unique setting this respect xenotransplantation, which human depend factors produced by other species, we will review. These insights should help assess deviations steady state actively protect improve recovery ecosystem situ optimally sustain healthy experimental clinical

Language: Английский

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Single‐cell transcriptomics of LepR‐positive skeletal cells reveals heterogeneous stress‐dependent stem and progenitor pools

The EMBO Journal, Journal Year: 2021, Volume and Issue: 41(4)

Published: Dec. 27, 2021

Language: Английский

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