Single-cell atlases: shared and tissue-specific cell types across human organs

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(7), P. 395 - 410

Published: Feb. 25, 2022

Language: Английский

---

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(4), P. 711 - 725.e6

Published: March 9, 2023

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but immunological mechanism and molecular determinants primary acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors bone marrow-residing cells multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that immune repertoire reacts therapy with state-dependent clonal expansion find evidence supporting coupling tumor recognition via major histocompatibility complex class I (MHC I), exhaustion, clinical response. abundance exhausted-like CD8+ clones be associated response failure, describe loss target epitope MHC as tumor-intrinsic adaptations TCEs. These findings advance our understanding vivo humans provide rationale for predictive immune-monitoring conditioning guide future immunotherapy hematological malignancies.

Language: Английский

---

Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging

Cell, Journal Year: 2024, Volume and Issue: 187(12), P. 3120 - 3140.e29

Published: May 6, 2024

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) profile 29,325 non-hematopoietic discovered nine transcriptionally distinct subtypes. simultaneously profiled 53,417 hematopoietic predicted their interactions with subsets. employed co-detection by indexing (CODEX) spatially over 1.2 million cells. integrated scRNA-seq CODEX data link cellular signaling proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, an adipocytic localization stem progenitor (HSPCs). our atlas annotate new images uncovered mesenchymal stromal cell (MSC) expansion neighborhoods co-enriched leukemic blasts MSCs acute myeloid leukemia (AML) patient samples. This resolved, multiomic provides reference investigation that drive

Language: Английский

---

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

---

Bone Marrow Niches of Hematopoietic Stem and Progenitor Cells

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4462 - 4462

Published: April 18, 2022

The mammalian hematopoietic system is remarkably efficient in meeting an organism's vital needs, yet highly sensitive and exquisitely regulated. Much of the organismal control over hematopoiesis comes from regulation stem cells (HSCs) by specific microenvironments called niches bone marrow (BM), where HSCs reside. experimental studies last two decades using most sophisticated advanced techniques have provided important data on identity niche controlling functions some mechanisms underlying niche-HSC interactions. In this review we discuss various aspects organization functioning HSC cell marrow. particular, anatomy BM niches, types composing niche, for more differentiated cells, metabolism relation to aging, leukemic transformation current state modeling vitro.

Language: Английский

---

Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis, and bone mass

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 13, 2023

M-CSF is a critical growth factor for myeloid lineage cells, including monocytes, macrophages, and osteoclasts. Tissue-resident macrophages in most organs rely on local M-CSF. However, it unclear what specific cells the bone marrow produce to maintain homeostasis. Here, we found that Adipoq-lineage progenitors but not mature adipocytes or peripheral adipose tissue, are major cellular source of M-CSF, with these producing at levels much higher than those produced by osteoblast cells. The high CSF1 expression also exist human marrow. Deficiency drastically reduces generation osteoclasts, leading severe osteopetrosis mice. Furthermore, osteoporosis ovariectomized mice can be significantly alleviated absence progenitors. Our findings identify as reveal their crucial contribution macrophage development, osteoclastogenesis, homeostasis, pathological loss.

Language: Английский

---

Single-cell RNA sequencing to track novel perspectives in HSC heterogeneity

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 29, 2022

Abstract As the importance of cell heterogeneity has begun to be emphasized, single-cell sequencing approaches are rapidly adopted study and cellular evolutionary relationships various cells, including stem populations. The hematopoietic progenitor (HSPC) compartment contains HSC cells (HSCs) distinct with different abilities self-renew. These perform their own functions maintain lineages. Undeniably, approaches, RNA (scRNA-seq) technologies, empower more opportunities normal pathological HSCs. In this review, we discuss how these scRNA-seq technologies contribute tracing origin lineage commitment HSCs, profiling bone marrow microenvironment providing high-resolution dissection malignant hematopoiesis, leading exciting new findings in biology.

Language: Английский

---

Developmental angiocrine diversification of endothelial cells for organotypic regeneration

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(22), P. 3042 - 3051

Published: Nov. 1, 2021

Language: Английский

---

O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 2, 2023

In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal growth ossification provide a microenvironment for transition definitive hematopoiesis; however, mechanisms orchestrating development of skeletal systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as posttranslational switch that dictates differentiation fate niche function early BM stromal cells (BMSCs). By modifying activating RUNX2, O-GlcNAcylation promotes osteogenic BMSCs IL-7 expression support lymphopoiesis. contrast, C/EBPβ-dependent adipogenesis myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in leads impaired formation, increased adiposity, well defective B-cell lymphopoiesis myeloid overproduction mice. Thus, balance adipogenic determined reciprocal regulation transcription factors, which simultaneously shapes niche.

Language: Английский

---

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 16, 2024

Abstract The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these and their spatial organization remain largely uncharacterized as they have been technically challenging study in humans. Here, we used fresh femoral head samples performed single-cell RNA sequencing (scRNA-Seq) profile 29,325 enriched discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy acute myeloid leukemia (AML) samples, spatially over one million single with a novel 53-antibody panel. discovered relatively hyperoxygenated arterio-endosteal niche early myelopoiesis, an adipocytic, but not endosteal or perivascular, hematopoietic stem progenitor cells. our atlas predict cell type labels new images predictions uncover mesenchymal stromal (MSC) expansion leukemic blast/MSC-enriched neighborhoods AML patient samples. Our work represents first comprehensive, spatially-resolved multiomic human will serve reference future investigation cellular interactions that drive

Language: Английский

---