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

被引：66

作者：

Bandyopadhyay, Shovik ^{[1
,2
]}

Duffy, Michael P. ^{[3
]}

Ahn, Kyung Jin ^{[4
,5
]}

Sussman, Jonathan H.

Pang, Minxing ^{[6
]}

Smith, David ^{[7
]}

Duncan, Gwendolyn ^{[8
]}

Zhang, Iris ^{[10
]}

Huang, Jeffrey ^{[8
]}

Lin, Yulieh ^{[3
]}

Xiong, Barbara ^{[2
,9
]}

Imtiaz, Tamjid ^{[4
,8
]}

Chen, Chia -Hui ^{[4
,5
]}

Thadi, Anusha ^{[4
,5
]}

Chen, Changya ^{[4
,5
]}

Xu, Jason ^{[2
,9
]}

Reichart, Melissa

Martinez, Zachary ^{[4
,5
]}

Diorio, Caroline ^{[4
,5
]}

Chen, Chider ^{[11
]}

Pillai, Vinodh ^{[12
]}

Snaith, Oraine ^{[12
]}

Oldridge, Derek ^{[12
]}

Bhattacharyya, Siddharth ^{[12
]}

Maillard, Ivan ^{[13
]}

Carroll, Martin ^{[13
]}

Nelson, Charles ^{[3
]}

Qin, Ling ^{[3
]}

Tan, Kai ^{[4
,7
,14
]}

机构：

[1] Univ Penn, Perelman Sch Med, Cellular & Mol Biol Grad Grp, Philadelphia, PA USA

[2] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA USA

[3] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA

[4] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[5] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA

[6] Univ Penn, Appl Math & Computat Sci Grad Grp, Philadelphia, PA USA

[7] Childrens Hosp Philadelphia, Ctr Single Cell Biol, Philadelphia, PA 19104 USA

[8] Univ Penn, Dept Bioengn, Philadelphia, PA USA

[9] Univ Penn, Perelman Sch Med, Genom & Computat Biol Grad Grp, Philadelphia, PA USA

[10] Univ Penn, Dept Comp & Informat Sci, Philadelphia, PA USA

[11] Univ Penn, Sch Dent Med, Dept Oral & Maxillofacial Surg & Pharmacol, Philadelphia, PA USA

[12] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA USA

[13] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA USA

[14] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA USA

来源：

CELL | 2024年 / 187卷 / 12期

基金：

美国国家卫生研究院;

关键词：

HEMATOPOIETIC STEM-CELLS; PROGENITOR; IDENTIFICATION; ADIPOCYTES; REGENERATION; MAINTENANCE; EXPRESSION; EMERGENCY; HALLMARK; VESSELS;

D O I：

10.1016/j.cell.2024.04.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：3120 / 3140.e29

页数：51

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