The dynamics of hematopoiesis over the human lifespan

被引：0

作者：

Li, Hojun ^{[1
,2
,3
,4
,5
,6
]}

Cote, Parker ^{[4
,5
]}

Kuoch, Michael ^{[4
]}

Ezike, Jideofor ^{[7
,8
]}

Frenis, Katie ^{[2
]}

Afanassiev, Anton ^{[9
]}

Greenstreet, Laura ^{[9
]}

Tanaka-Yano, Mayuri ^{[2
,3
]}

Tarantino, Giuseppe ^{[10
]}

Zhang, Stephen ^{[9
]}

Whangbo, Jennifer ^{[1
,2
,3
,11
]}

Butty, Vincent L. ^{[12
]}

Moiso, Enrico ^{[4
]}

Falchetti, Marcelo ^{[13
,14
]}

Lu, Kate ^{[4
]}

Connelly, Guinevere G. ^{[4
]}

Morris, Vivian ^{[2
]}

Wang, Dahai ^{[2
]}

Chen, Antonia F. ^{[3
,15
]}

Bianchi, Giada ^{[3
,10
]}

Daley, George Q. ^{[2
,3
]}

Garg, Salil ^{[4
,16
]}

Liu, David ^{[3
,10
]}

Chou, Stella T. ^{[17
,18
]}

Regev, Aviv ^{[6
,19
]}

Lummertz da Rocha, Edroaldo ^{[13
,14
]}

Schiebinger, Geoffrey ^{[9
]}

Rowe, R. Grant ^{[1
,2
,3
]}

机构：

[1] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[2] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[5] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA

[6] Rady Childrens Hosp, Div Hematol Oncol, San Diego, CA 92123 USA

[7] MIT, Computat & Syst Biol Program, Cambridge, MA USA

[8] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA USA

[9] Univ British Columbia, Dept Math, Vancouver, BC, Canada

[10] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA

[11] Vor Biopharm, Cambridge, MA USA

[12] Koch Inst, Barbara K Ostrom Bioinformat Facil, Integrated Genom & Bioinformat Core, Cambridge, MA USA

[13] Univ Fed Santa Catarina, Dept Microbiol, Florianopolis, SC, Brazil

[14] Univ Fed Santa Catarina, Dept Immunol & Parasitol, Florianopolis, SC, Brazil

[15] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA USA

[16] Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA

[17] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USA

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

[19] Genentech South San Francisco, San Francisco, CA USA

来源：

NATURE METHODS | 2025年 / 22卷 / 02期

基金：

加拿大自然科学与工程研究理事会;

关键词：

SINGLE-CELL ANALYSIS; STEM-CELLS; GENE-EXPRESSION; UP-REGULATION; REVEALS; MICROENVIRONMENT;

D O I：

10.1038/s41592-024-02495-0

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Over a lifetime, hematopoietic stem cells (HSCs) adjust their lineage output to support age-aligned physiology. In model organisms, stereotypic waves of hematopoiesis have been observed corresponding to defined age-biased HSC hallmarks. However, how the properties of hematopoietic stem and progenitor cells change over the human lifespan remains unclear. To address this gap, we profiled individual transcriptome states of human hematopoietic stem and progenitor cells spanning gestation, maturation and aging. Here we define the gene expression networks dictating age-specific differentiation of HSCs and the dynamics of fate decisions and lineage priming throughout life. We additionally identifiy and functionally validate a fetal-specific HSC state with robust engraftment and multilineage capacity. Furthermore, we observe that classification of acute myeloid leukemia against defined transcriptional age states demonstrates that utilization of early life transcriptional programs associates with poor prognosis. Overall, we provide a disease-relevant framework for heterochronic orientation of stem cell ontogeny along the real time axis of the human lifespan. This Resource presents an atlas classifying the age-related changes in human hematopoietic stem and progenitor cells from gestation through aging.

引用

页码：422 / 434

页数：38

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