Machine Learning of Hematopoietic Stem Cell Divisions from Paired Daughter Cell Expression Profiles Reveals Effects of Aging on Self-Renewal

Arai, Fumio; Stumpf, Patrick S.; Ikushima, Yoshiko Matsumoto; Hosokawa, Kentaro; Roch, Aline; Suda, Toshio; MacArthur, Ben D.

doi:10.1016/j.cels.2020.11.004

Cited by 13 publications

(18 citation statements)

References 89 publications

(110 reference statements)

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“…The Evi1 expression level predicts HSC capacity; therefore, we monitored Evi1 expression following genome editing of HSCs from Evi1-GFP mice. 70 , 71 The frequency of Evi1-GFP + cells was inversely correlated with the cytokine concentration in culture without electroporation and was highest upon culture in the presence of 0.5 ng/mL SCF and 1 ng/mL TPO ( Figure S3 E). Consistently, the frequency of Evi1-GFP + cells within the CD48 − LSK fraction ( Figure 3 J) was lower under the proliferative condition than under the quiescence-maintaining condition.…”

Section: Resultsmentioning

confidence: 99%

A culture platform to study quiescent hematopoietic stem cells following genome editing

Shiroshita

Kobayashi

Watanuki

et al. 2022

Cell Reports Methods

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Section: Resultsmentioning

confidence: 99%

A culture platform to study quiescent hematopoietic stem cells following genome editing

Shiroshita

Kobayashi

Watanuki

et al. 2022

Cell Reports Methods

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“…One potential limitation of our study is that we have not looked into how HSC divisions are regulated. Recent reports suggest that the HSC niche plays a major role and ageing is a critical regulator of this process 14,48,49 . Further investigation into deciphering the mechanism shall allow controlling HSC division types, and eventually HSC pool size.…”

Section: Discussionmentioning

confidence: 99%

“…These age-associated changes in HSCs have been functionally validated using transplantation assays 8,9,10,11,12 , but quantitative assessment to date has been limited. To simultaneously maintain the HSC pool and differentiated progenies, HSCs must regulate their cell division in response to environmental cues 13,14,15,16 . Asymmetric cell divisions (one self-renewing daughter cell and one differentiated daughter cell) are known to maintain tissue homeostasis 17 .…”

mentioning

confidence: 99%

Age-related changes in the haematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

Kawahigashi

Iwanami

Takahashi

et al. 2022

Preprint

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Haematopoietic stem cells (HSCs) are somatic stem cells that continuously generate lifelong supply of blood cells through a balance of symmetric and asymmetric divisions. Recently, it is well established that the HSC pool increases with age. However, not much is known about the underlying cause for these observed changes. Here, using a novel method combining single-cell ex vivo HSC expansion with mathematical modeling, we quantify HSC division types (stem cell - stem cell (S-S) division, stem cell - progenitor cell (S-P) division, and progenitor cell - progenitor cell (P-P) division) as a function of the ageing process. Our time-series experiments reveal how changes in these three modes of division can explain the increase in HSC numbers with age. Contrary to the popular notion that HSCs divide predominantly through S-P divisions, we show that S-S divisions are predominant throughout the lifespan of the animal, thereby expanding the HSC pool. We, therefore, provide a novel mathematical model-based experimental validation for reflecting HSC dynamics in vivo.

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“…An increase in age marks a decrease in trimethylation of histone3 at lysine 27 and 9 (H3K9me27 and H3K9me3) and acetylation at lysine 9 (H3K9Ac). This leads to defective vascular repair and hematopoietic stem-cell dysfunction [79]. In aging, enhanced miRNA expression leads to suppression of PTMs (post-transcriptional modifications) of target genes and changes in endothelial functions.…”

Section: Agingmentioning

confidence: 99%

Studying Epigenetics of Cardiovascular Diseases on Chip Guide

et al. 2022

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Epigenetics is defined as the study of inheritable changes in the gene expressions and phenotypes that occurs without altering the normal DNA sequence. These changes are mainly due to an alteration in chromatin or its packaging, which changes the DNA accessibility. DNA methylation, histone modification, and noncoding or microRNAs can best explain the mechanism of epigenetics. There are various DNA methylated enzymes, histone-modifying enzymes, and microRNAs involved in the cause of various CVDs (cardiovascular diseases) such as cardiac hypertrophy, heart failure, and hypertension. Moreover, various CVD risk factors such as diabetes mellitus, hypoxia, aging, dyslipidemia, and their epigenetics are also discussed together with CVDs such as CHD (coronary heart disease) and PAH (pulmonary arterial hypertension). Furthermore, different techniques involved in epigenetic chromatin mapping are explained. Among these techniques, the ChIP-on-chip guide is explained with regard to its role in cardiac hypertrophy, a final form of heart failure. This review focuses on different epigenetic factors that are involved in causing cardiovascular diseases.

show abstract

Machine Learning of Hematopoietic Stem Cell Divisions from Paired Daughter Cell Expression Profiles Reveals Effects of Aging on Self-Renewal

Cited by 13 publications

References 89 publications

A culture platform to study quiescent hematopoietic stem cells following genome editing

A culture platform to study quiescent hematopoietic stem cells following genome editing

Age-related changes in the haematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

Studying Epigenetics of Cardiovascular Diseases on Chip Guide

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