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研究领域生物医学和临床科学心血管医学和血液学血液学
MYCT1控制人类造血干细胞中的环境传感

MYCT1控制人类造血干细胞中的环境传感

Júlia Aguadé-Gorgorió ^1,2, Yasaman Jami-Alahmadi ^3,4, Vincenzo Calvanese ^5,6,7,8, Maya Kardouh ^5,9, Iman Fares ^5,10, Haley Johnson ^5,11, Valerie Rezek ^6,12,13, Feiyang Ma ^5,14,15, Mattias Magnusson ^5,6,16, Yanling Wang ⁵, Juliana E Shin ^17,12, Karina J Nance ¹⁷, Helen S Goodridge ^12,17, Simone Liebscher ¹⁸, Katja Schenke-Layland ^18,19, Gay M Crooks ^6,20,21, James A Wohlschlegel ³, Hanna K A Mikkola ^22,23,24,25

Júlia Aguadé-Gorgorió ^1,2, Yasaman Jami-Alahmadi ^3,4, Vincenzo Calvanese ^5,6,7,8

¹Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA. julia.aguade@gmail.com.
²Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA. julia.aguade@gmail.com.
³Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, USA.
⁴Pfizer, Cambridge, MA, USA.
⁵Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
⁶Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
⁷Laboratory for Molecular Cell Biology, University College London, London, UK.
⁸Josep Carreras Leukaemia Research Institute, Barcelona, Spain.
⁹Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
¹⁰Kite Pharma, Santa Monica, CA, USA.
¹¹Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
¹²David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹³UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵Amgen, Thousand Oaks, CA, USA.
¹⁶Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
¹⁷Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁸Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University, Tübingen, Germany.
¹⁹NMI Natural and Medical Sciences Institute at the University Tübingen, Reutlingen, Germany.
²⁰Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
²¹Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
²²Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA. hmikkola@mcdb.ucla.edu.
²³Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA. hmikkola@mcdb.ucla.edu.
²⁴Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. hmikkola@mcdb.ucla.edu.
²⁵Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA. hmikkola@mcdb.ucla.edu.

⁰Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA. julia.aguade@gmail.com.

Nature +

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2024年六月5日

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在PubMed上查看摘要

概括

此摘要是机器生成的。

MYC目标1 (MYCT1) 通过缓解内细胞分裂来调节人类造血干细胞 (HSC) 的自我更新. 恢复MYCT1可以改善HSC的扩张和移植,这对树干的保存至关重要.

科学领域

血液学
干细胞生物学
分子生物学

背景情况

人体造血干细胞 (HSC) 的自我更新和移植是很难理解的,并且很难在培养中复制.
目前的方法难以可靠地扩展功能性HSC用于治疗.

研究的目的

确定人体HSC自我更新和移植的关键调节者.
调查MYC目标1 (MYCT1) 在培养过程中维持HSC茎的作用.

主要方法

人类胎儿肝脏和带血 (CB) 血造干细胞和前代细胞 (HSPC) 中的MYCT1中断和过度表达.
单细胞RNA测序以分析基因表达变化.
用于评估HSPC扩张,移植,内细胞化率和线粒体活动.

主要成果

在未分化HSPC中选择性表达MYCT1并在培养过程中下调.
MYCT1的倒置影响了HSPC的扩张和植入.
恢复MYCT1表达增强了培养CBHSPC的扩张和移植.
MYCT1调节了ETS因子的表达,线粒体活动和内细胞分裂,从而保持了HSC的干性.

结论

MYCT1是人类HSC干的关键调节者,缓和内细胞和环境感应.
在培养过程中MYCT1的下调是危及HSC扩张的漏洞.
针对MYCT1提供了改善HSC扩展和治疗应用的潜在策略.

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相关概念视频

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Multipotency of Hematopoietic Stem Cells

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...

Lineage Commitment

Lineage Commitment

Commitment is the process whereby stem cells:

lose their ability to form all cell types and
irreversibly change into a specific type.

The multipotent hematopoietic stem cells, (HSCs), differentiate into the multipotent hematopoietic progenitor cells, (HPCs). The HPCs express many lineage-specific cytokine receptors. Each of these receptors binds specific cytokines, activates distinct signaling pathways, and expresses a particular gene set. The HPCs further differentiate to...

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

Hematopoiesis

Hematopoiesis

The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...

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